Innate and adaptive immune responses of the central nervous system

Critical Reviews in Immunology

Volumn 26, Issue 2, 2006, Pages 149-188

  Bailey, Samantha L ^a   Carpentier, Pamela A ^a   McMahon, Eileen J ^b   Begolka, Wendy Smith ^a   Miller, Stephen D ^a  

^a NORTHWESTERN UNIVERSITY   (United States)

^b WESTMONT COLLEGE   (United States)

Author keywords

Astrocyte; CD4+ Th1 cell; Cerebrovascular endothelial cell; Dendritic cell; Macrophage; Microglia

Indexed keywords

ANTIGEN; CD4 ANTIGEN; CELL ADHESION MOLECULE; CHEMOKINE; MAJOR HISTOCOMPATIBILITY ANTIGEN; MATRIX METALLOPROTEINASE; MYELIN;

ADAPTIVE IMMUNITY; ANTIGEN PRESENTING CELL; ASTROCYTE; AUTOIMMUNITY; BLOOD BRAIN BARRIER; BRAIN BLOOD VESSEL; CD4+ T LYMPHOCYTE; CELL FUNCTION; CELL INFILTRATION; CELL TRANSPORT; CENTRAL NERVOUS SYSTEM; CYTOKINE PRODUCTION; DENDRITIC CELL; ENDOTHELIUM CELL; EVOLUTION; HUMAN; IMMUNE DEFICIENCY; IMMUNE RESPONSE; IMMUNITY; IMMUNOMODULATION; IMMUNOSURVEILLANCE; INNATE IMMUNITY; LEUKOCYTE MIGRATION; LYMPHATIC DRAINAGE; MACROPHAGE; MAJOR HISTOCOMPATIBILITY COMPLEX; MICROGLIA; MOLECULE; NEUROIMMUNOLOGY; NEUROPATHOLOGY; NONHUMAN; PRIORITY JOURNAL; PROTEIN EXPRESSION; REGULATORY MECHANISM; REVIEW; TH1 CELL; TISSUE STRUCTURE; VASCULAR ENDOTHELIUM; ANIMAL; AUTOIMMUNE DISEASE; BIOLOGICAL MODEL; CYTOLOGY; IMMUNOLOGY;

ANIMALS; ASTROCYTES; AUTOIMMUNE DISEASES; BLOOD-BRAIN BARRIER; CD4-POSITIVE T-LYMPHOCYTES; CENTRAL NERVOUS SYSTEM; DENDRITIC CELLS; ENDOTHELIAL CELLS; HUMANS; IMMUNITY, NATURAL; IMMUNOLOGIC SURVEILLANCE; MACROPHAGES; MICROGLIA; MODELS, IMMUNOLOGICAL;

EID: 33744975502     PISSN: 10408401     EISSN: None     Source Type: Journal    
DOI: 10.1615/critrevimmunol.v26.i2.40     Document Type: Review

References (450)

1. Anderson AC, Nicholson LB, Legge KL, Turchin V, Zaghouani H, Kuchroo VK. High frequency of autoreactive myelin proteolipid protein-specific T cells in the periphery of naive mice: mechanisms of selection of the self-reactive repertoire. J Exp Med. 2000;191:761-70.
2. Miller SD, McRae BL, Vanderlugt CL, Nikcevich KM, Pope JG, Pope L, Karpus WJ. Evolution of the T cell repertoire during the course of experimental autoimmune encephalomyelitis. Immunol Rev. 1995;144:225-44.
3. Zhang J, Markovic-Plese S, Lacet B, Raus J, Weiner HL, Hafler DA. Increased frequency of interleukin 2-responsive T cells specific for myelin basic protein and proteolipid protein in peripheral blood and cerebrospinal fluid of patients with multiple sclerosis. J Exp Med. 1994;179:973-84.
4. Reddy J, Bettelli E, Nicholson L, Waldner H, Jang MH, Wucherpfennig KW, Kuchroo VK. Detection of autoreactive myelin proteolipid protein 139-151-specific T cells by using MHC II (IAs) tetramers. J Immunol. 2003;170:870-7.
5. Wekerle H. Immunopathogenesis of multiple sclerosis. Acta Neurologica. 1991;13:197-204.
6. Gonatas NK, Greene MI, Waksman BH. Genetic and molecular aspects of demyelination. Immunol Today. 1986;7:121-6.
7. Miller SD, Vanderlugt CL, Begolka WS, Pao W, Yauch RL, Neville KL, Katz-Levy Y, Carrizosa A, Kim BS. Persistent infection with Theiler's virus leads to CNS autoimmunity via epitope spreading. Nat Med. 1997;3:1133-6.
8. McRae BL, Vanderlugt CL, Dal Canto MC, Miller SD. Functional evidence for epitope spreading in the relapsing pathology of experimental autoimmune encephalomyelitis. J Exp Med. 1995;182:75-85.
9. Kurtzke JF. Epidemiologic evidence for multiple sclerosis as an infection. Clin Microbiol Rev. 1993;6:382-427.
10. Miller SD, Gerety SJ, Kennedy MK, Peterson JD, Trotter JL, Tuohy VK, Waltenbaugh C, Dal Canto MC, Lipton HL. Class II-restricted T cell responses in Theiler's murine encephalomyelitis virus (TMEV)-induced demyelinating disease. III. Failure of neuro-antigen-specific immune tolerance to affect the clinical course of demyelination. J Neuroimmunol. 1990;26:9-23.
11. Lipton HL, Gonzalez-Scarano F. Central nervous system immunity in mice infected with Theiler's virus. I. Local neutralizing antibody response. J Infect Dis. 1978;137:145-51.
12. Dal Canto MC, Barbano RL. Immunocytochemical localization of MAG, MBP and P0 protein in acute and relapsing demyelinating lesions of Theiler's virus infection. J Neuroimmunol. 1985;10:129-40.
13. - T lymphocytes. J Immunol. 1981;127:1420-3.
14. McMahon EJ, Bailey SL, Castenada CV, Waldner H, Miller SD. Epitope spreading initiates in the CNS in two mouse models of multiple sclerosis. Nat Med. 2005;11:335-9.
15. Greter M, Heppner FL, Lemos MP, Odermatt BM, Goebels N, Laufer T, Noelle RJ, Becher B. Dendritic cells permit immune invasion of the CNS in an animal model of multiple sclerosis. Nat Med. 2005;11:328-34.
16. Steinman RM. The dendritic cell system and its role in immunogenicity. Ann Rev Immunol. 1991;9:271-96.
17. Geyer SJ, Gill TJ III, Kunz HW, Moody E. Immunogenetic aspects of transplantation in the rat brain. Transplantation. 1985;39:244-7.
18. Head JR, Griffin WS. Functional capacity of solid tissue transplants in the brain: evidence for immunological privilege. Proc Royal Soc London-Series B: Biol Sci. 1985;224:375-87.
19. Male DK, Pryce G, Hughes CC. Antigen presentation in brain: MHC induction on brain endothelium and astrocytes compared. Immunology. 1987;60:453-9.
20. Traugott U, Lebon P. Interferon-gamma and Ia antigen are present on astrocytes in active chronic multiple sclerosis lesions. J Neurol Sci. 1988;84:257-64.
21. Prat A, Biernacki K, Wosik K, Antel JP. Glial cell influence on the human blood-brain barrier. Glia. 2001;36:145-55.
22. Pachter JS, de Vries HE, Fabry Z. The blood-brain barrier and its role in immune privilege in the central nervous system. J Neuropathol Exp Neurol. 2003;62:593-604.
23. Staddon JM, Rubin LL. Cell adhesion, cell junctions and the blood-brain barrier. Curr Opin Neurobiol. 1996;6:622-7.
24. Ballabh P, Braun A, Nedergaard M. The blood-brain barrier: an overview: structure, regulation, and clinical implications. Neurobiol Dis. 2004;16:1-13.
25. Hickey WF. Leukocyte traffic in the central nervous system: the participants and their roles. Semin Immunol. 1999;11:125-37.
26. Neuhaus J, Risau W, Wolburg H. Induction of blood-brain barrier characteristics in bovine brain endothelial cells by rat astroglial cells in transfilter coculture. Ann N Y Acad Sci. 1991;633:578-80.
27. Tao-Cheng JH, Nagy Z, Brightman MW. Tight junctions of brain endothelium in vitro are enhanced by astroglia. J Neurosci. 1987;7:3293-9.
28. Hayashi Y, Nomura M, Yamagishi S, Harada S, Yamashita J, Yamamoto H. Induction of various blood-brain barrier properties in non-neural endothelial cells by close apposition to co-cultured astrocytes. Glia. 1997;19:13-26.
29. Rubin LL, Barbu K, Bard F, Cannon C, Hall DE, Horner H, Janatpour M, Liaw C, Manning K, Morales J. Differentiation of brain endothelial cells in cell culture. Ann N Y Acad Sci. 1991;633:420-5.
30. Janzer RC, Raff MC. Astrocytes induce blood-brain barrier properties in endothelial cells. Nature. 1987;325:253-7.
31. Abbott NJ. Astrocyte-endothelial interactions and blood-brain barrier permeability. J Anat. 2002;200:629-38.
32. Guillemin GJ, Brew BJ. Microglia, macrophages, perivascular macrophages, and pericytes: a review of function and identification. J Leukoc Biol. 2004;75:388-97.
33. Ramsauer M, Krause D, Dermietzel R. Angiogenesis of the blood-brain barrier in vitro and the function of cerebral pericytes. FASEB J. 2002;16:1274-6.
34. Angelov DN, Walther M, Streppel M, Guntinas-Lichius O, Neiss WF. The cerebral perivascular cells. Adv Anat Embryol Cell Biol. 1998;147:1-87.
35. Balabanov R, Dore-Duffy P. Role of the CNS microvascular pericyte in the blood-brain barrier. J Neurosci Res. 1998;53:637-44.
36. Kida S, Steart PV, Zhang ET, Weller RO. Perivascular cells act as scavengers in the cerebral perivascular spaces and remain distinct from pericytes, microglia and macrophages. Acta Neuropathol (Berl). 1993;85:646-52.
37. Hickey WF. Basic principles of immunological surveillance of the normal central nervous system. Glia. 2001;36:118-24.
38. Hickey WF, Hsu BL, Kimura H. T lymphocyte entry into the central nervous system. J Neurosci Res. 1991;28:254-60.
39. Carrithers MD, Visintin I, Kang SJ, Janeway CA. Differential adhesion molecule requirements for immune surveillance and inflammatory recruitment. Brain. 2000;123(Pt 6):1092-101.
40. Carrithers MD, Visintin I, Viret C, Janeway CS Jr. Role of genetic background in P selectin-dependent immune surveillance of the central nervous system. J Neuroimmunol. 2002;129:51-7.
41. Kivisakk P, Mahad DJ, Callahan MK, Trebst C, Tucky B, Wei T, Wu L, Baekkevold ES, Lassmann H, Staugaitis SM, Campbell JJ, Ransohoff RM. Human cerebrospinal fluid central memory CD4+ T cells: evidence for trafficking through choroid plexus and meninges via P-selectin. Proc Natl Acad Sci U S A. 2003;100:8389-94.
42. Oehmichen M, Gruninger H, Wietholter H, Gencic M. Lymphatic efflux of intracerebrally injected cells. Acta Neuropathol (Berl). 1979;45:61-5.
43. Bradbury MW, Cserr HF, Westrop RJ. Drainage of cerebral interstitial fluid into deep cervical lymph of the rabbit. Am J Physiol. 1981;240:F329-F36.
44. Ransohoff RM, Kivisakk P, Kidd G. Three or more routes for leukocyte migration into the central nervous system. Nat Rev Immunol. 2003;3:569-81.
45. Hochwald GM, Van DA, Robinson ME, Thorbecke GJ. Immune response in draining lymph nodes and spleen after intraventricular injection of antigen. Int J Neurosci. 1988;39:299-306.
46. Yamada S, DePasquale M, Patlak CS, Cserr HF. Albumin outflow into deep cervical lymph from different regions of rabbit brain. Am J Physiol. 1991;261:H1197-H204.
47. Kida S, Pantazis A, Weller RO. CSF drains directly from the subarachnoid space into nasal lymphatics in the rat. Anatomy, histology and immunological significance. Neuropathol Appl Neurobiol. 1993;19:480-8.
48. Muldoon LL, Varallyay P, Kraemer DF, Kiwic G, Pinkston K, Walker-Rosenfeld SL, Neuwelt EA. Trafficking of superparamagnetic iron oxide particles (Combidex) from brain to lymph nodes in the rat. Neuropathol Appl Neurobiol. 2004;30:70-9.
49. Vega JL, Jonakait GM. The cervical lymph nodes drain antigens administered into the spinal subarachnoid space of the rat. Neuropathol Appl Neurobiol. 2004;30:416-8.
50. Widner H, Moller G, Johansson BB. Immune response in deep cervical lymph nodes and spleen in the mouse after antigen deposition in different intracerebral sites. Scand J Immunol. 1988;28:563-71.
51. Cserr HF, Harling-Berg CJ, Knopf PM. Drainage of brain extracellular fluid into blood and deep cervical lymph and its immunological significance. Brain Pathol. 1992;2:269-76.
52. Harling-Berg CJ, Park TJ, Knopf PM. Role of the cervical lymphatics in the Th2-type hierarchy of CNS immune regulation. J Neuroimmunol. 1999;101:111-27.
53. Knopf PM, Harling-Berg CJ, Cserr HF, Basu D, Sirulnick EJ, Nolan SC, Park JT, Keir G, Thompson EJ, Hickey WF. Antigen-dependent intrathecal anti-body synthesis in the normal rat brain: tissue entry and local retention of antigen-specific B cells. J Immunol. 1998;161:692-701.
54. Qing Z, Sewell D, Sandor M, Fabry Z. Antigen-specific T cell trafficking into the central nervous system. J Neuroimmunol. 2000;105:169-78.
55. Ling C, Sandor M, Fabry Z. In situ processing and distribution of intracerebrally injected OVA in the CNS. J Neuroimmunol. 2003;141:90-8.
56. Liu W, Brosnan CF, Dickson DW, Lee SC. Macrophage colony-stimulating factor mediates astrocyte-induced microglial ramification in human fetal central nervous system culture. Am J Pathol. 1994;145:48-53.
57. Constam DB, Philipp J, Malipiero UV, ten Dijke P, Schachner M, Fontana A. Differential expression of transforming growth factor-beta 1, -beta 2, and -beta 3 by glioblastoma cells, astrocytes, and microglia. J Immunol. 1992;148:1404-10.
58. Peress NS, Perillo E, Seidman RJ. Glial transforming growth factor (TGF)-beta isotypes in multiple sclerosis: differential glial expression of TGF-beta 1, 2 and 3 isotypes in multiple sclerosis. J Neuroimmunol. 1996;71:115-23.
59. Hetier E, Ayala J, Bousseau A, Prochiantz A. Modulation of interleukin-1 and tumor necrosis factor expression by beta-adrenergic agonists in mouse ameboid microglial cells. Exp Brain Res. 1991;86:407-13.
60. Kim WK, Kan Y, Ganea D, Hart RP, Gozes I, Jonakait GM. Vasoactive intestinal peptide and pituitary adenylyl cyclase-activating polypeptide inhibit tumor necrosis factor-alpha production in injured spinal cord and in activated microglia via a cAMP-dependent pathway. J Neurosci. 2000;20:3622-30.
61. White CA, McCombe PA, Pender MP. Microglia are more susceptible than macrophages to apoptosis in the central nervous system in experimental autoimmune encephalomyelitis through a mechanism not involving Fas (CD95). Int Immunol. 1998;10:935-41.
62. Nguyen KB, McCombe PA, Pender MP. Macrophage apoptosis in the central nervous system in experimental autoimmune encephalomyelitis. J Autoimmun. 1994;7:145-52.
63. Bonetti B, Pohl J, Gao YL, Raine CS. Cell death during autoimmune demyelination: effector but not target cells are eliminated by apoptosis. J Immunol. 1997;159:5733-41.
64. Wei R, Jonakait GM. Neurotrophins and the anti-inflammatory agents interleukin-4 (IL-4), IL-10, IL-11 and transforming growth factor-betal (TGF-beta1) down-regulate T cell costimulatory molecules B7 and CD40 on cultured rat microglia. J Neuroimmunol. 1999;95:8-18.
65. O'Keefe GM, Nguyen VT, Benveniste EN. Class II transactivator and class II MHC gene expression in microglia: modulation by the cytokines TGF-beta, IL-4, IL-13 and IL-10. Eur J Immunol. 1999;29:1275-85.
66. Neumann H, Boucraut J, Hahnel C, Misgeld T, Wekerle H. Neuronal control of MHC class II inducibility in rat astrocytes and microglia. Eur J Neurosci. 1996;8:2582-90.
67. Neumann H, Misgeld T, Matsumuro K, Wekerle H. Neurotrophins inhibit major histocompatibility class II inducibility of microglia: involvement of the p75 neurotrophin receptor. Proc Natl Acad Sci U S A. 1998;95:5779-84.
68. Wright GJ, Puklavec MJ, Willis AC, Hoek RM, Sedgwick JD, Brown MH, Barclay AN. Lymphoid/neuronal cell surface OX2 glycoprotein recognizes a novel receptor on macrophages implicated in the control of their function. Immunity. 2000;13:233-42.
69. Hoek RM, Ruuls SR, Murphy CA, Wright GJ, Goddard R, Zurawski SM, Blom B, Homola ME, Streit WJ, Brown MH, Barclay AN, Sedgwick JD. Down-regulation of the macrophage lineage through interaction with OX2 (CD200). Science. 2000;290:1768-71.
70. Wenkel H, Streilein JW, Young MJ. Systemic immune deviation in the brain that does not depend on the integrity of the blood-brain barrier. J Immunol. 2000;164:5125-31.
71. Prud'homme GJ, Piccirillo CA. The inhibitory effects of transforming growth factor-beta-1 (TGF-beta1) in autoimmune diseases. J Autoimmun. 2000;14:23-42.
72. Ford AL, Foulcher E, Lemckert FA, Sedgwick JD. Microglia induce CD4 T lymphocyte final effector function and death. J Exp Med. 1996;184:1737-45.
73. Gimsa U, Oren A, Pandiyan P, Teichmann D, Bechmann I, Nitsch R, Brunner-Weinzierl MC. Astrocytes protect the CNS: antigen-specific T helper cell responses are inhibited by astrocyte-induced upregulation of CTLA-4 (CD152). J Mol Med. 2004;82:364-72.
74. Meinl E, Aloisi F, Ertl B, Weber F, De Waal Malefyt R, Wekerle H, Hohlfeld R. Multiple sclerosis. Immunomodulatory effects of human astrocytes on T cells. Brain. 1994;117:1323-32.
75. Sun DM, Coleclough C, Whitaker JN. Nonactivated astrocytes downregulate T cell receptor expression and reduce antigen-specific proliferation and cytokine production of myelin basic protein (MBP)-reactive T cells. J Neuroimmunol. 1997;78:69-78.
76. Xiao BG, Diab A, Zhu J, van der Meide P, Link H. Astrocytes induce hyporesponses of myelin basic protein-reactive T and B cell function. J Neuroimmunol. 1998;89:113-21.
77. Trajkovic V, Vuckovic O, Stosic-Grujicic S, Miljkovic D, Popadic D, Markovic M, Bumbasirevic V, Backovic A, Cvetkovic I, Harhaji L, Ramie Z, Mostarica SM. Astrocyte-induced regulatory T cells mitigate CNS autoimmunity. Glia. 2004;47:168-79.
78. Pender MP, Rist MJ. Apoptosis of inflammatory cells in immune control of the nervous system: role of glia. Glia. 2001;36:137-44.
79. Bechmann I, Mor G, Nilsen J, Eliza M, Nitsch R, Naftolin F. FasL (CD95L, Apo1L) is expressed in the normal rat and human brain: evidence for the existence of an immunological brain barrier. Glia. 1999;27:62-74.
80. Frigerio S, Silei V, Ciusani E, Massa G, Lauro GM, Salmaggi A. Modulation of fas-ligand (Fas-L) on human microglial cells: an in vitro study. J Neuroimmunol. 2000;105:109-14.
81. Flugel A, Schwaiger FW, Neumann H, Medana I, Willem M, Wekerle H, Kreutzberg GW, Graeber MB. Neuronal FasL induces cell death of encephalitogenic T lymphocytes. Brain Pathol. 2000;10:353-64.
82. Bechmann I, Steiner B, Gimsa U, Mor G, Wolf S, Beyer M, Nitsch R, Zipp F. Astrocyte-induced T cell elimination is CD95 ligand dependent. J Neuroimmunol. 2002;132:60-5.
83. Kohji T, Tanuma N, Aikawa Y, Kawazoe Y, Suzuki Y, Kohyama K, Matsumoto Y. Interaction between apoptotic cells and reactive brain cells in the central nervous system of rats with autoimmune encephalomyelitis. J Neuroimmunol. 1998;82:168-74.
84. Bush TG, Puvanachandra N, Horner CH, Polito A, Ostenfeld T, Svendsen CN, Mucke L, Johnson MH, Sofroniew MV. Leukocyte infiltration, neuronal degeneration, and neurite outgrowth after ablation of scar-forming, reactive astrocytes in adult transgenic mice. Neuron. 1999;23:297-308.
85. Faulkner JR, Herrmann JE, Woo MJ, Tansey KE, Doan NB, Sofroniew MV. Reactive astrocytes protect tissue and preserve function after spinal cord injury. J Neurosci. 2004;24:2143-55.
86. Liedtke W, Edelmann W, Bieri PL, Chiu FC, Cowan NJ, Kucherlapati R, Raine CS. GFAP is necessary for the integrity of CNS white matter architecture and long-term maintenance of myelination. Neuron. 1996;17:607-15.
87. McCall MA, Gregg RG, Behringer RR, Brenner M, Delaney CL, Galbreath EJ, Zhang CL, Pearce RA, Chiu SY, Messing A. Targeted deletion in astrocyte intermediate filament (Gfap) alters neuronal physiology. Proc Natl Acad Sci U S A. 1996;93:6361-6.
88. Liedtke W, Edelmann W, Chiu FC, Kucherlapati R, Raine CS. Experimental autoimmune encephalomyelitis in mice lacking glial fibrillary acidic protein is characterized by a more severe clinical course and an infiltrative central nervous system lesion. Am J Pathol. 1998;152:251-9.
89. Stenzel W, Soltek S, Schluter D, Deckert M. The intermediate filament GFAP is important for the control of experimental murine Staphylococcus aureus-induced brain abscess and Toxoplasma encephalitis. J Neuropathol Exp Neurol. 2004;63:631-40.
90. Janeway CA Jr, Medzhitov R. Innate immune recognition. Annu Rev Immunol. 2002;20:197-216.
91. Barton GM, Medzhitov R. Toll-like receptors and their ligands. Curr Top Microbiol Immunol. 2002;270:81-92.
92. Zhang D, Zhang G, Hayden MS, Greenblatt MB, Bussey C, Flavell RA, Ghosh S. A toll-like receptor that prevents infection by uropathogenic bacteria. Science. 2004;303:1522-6.
93. Poltorak A, He X, Smirnova I, Liu MY, van Huffel C, Du X, Birdwell D, Alejos E, Silva M, Galanos C, Freudenberg M, Ricciardi-Castagnoli P, Layton B, Beutler B. Defective LPS signaling in C3H/HeJ and C57BL/10ScCr mice: mutations in Tlr4 gene. Science. 1998;282:2085-8.
94. Alexopoulou L, Holt AC, Medzhitov R, Flavell RA. Recognition of double-stranded RNA and activation of NF-kappaB by Toll-like receptor 3. Nature. 2001;413:732-8.
95. Stuehr DJ. Mammalian nitric oxide synthases. Biochim Biophys Acta. 1999;1411:217-30.
96. Bogdan C, Rollinghoff M, Diefenbach A. Reactive oxygen and reactive nitrogen intermediates in innate and specific immunity. Curr Opin Immunol. 2000;12:64-76.
97. Smith KJ, Kapoor R, Felts PA. Demyelination: the role of reactive oxygen and nitrogen species. Brain Pathol. 1999;9:69-92.
98. John GR, Lee SC, Song X, Rivieccio M, Brosnan CF. IL-1-regulated responses in astrocytes: relevance to injury and recovery. Glia. 2005;49:161-76.
99. Van Wagoner NJ, Benveniste EN. Interleukin-6 expression and regulation in astrocytes. J Neuroimmunol. 1999;100:124-39.
100. Hofman FM, Dohadwala MM, Wright AD, Hinton DR, Walker SM. Exogenous tat protein activates central nervous system-derived endothelial cells. J Neuroimmunol. 1994;54:19-28.
101. Vadeboncoeur N, Segura M, Al Numani D, Vanier G, Gottschalk M. Pro-inflammatory cytokine and chemokine release by human brain microvascular endothelial cells stimulated by Streptococcus suis serotype 2. FEMS Immunol Med Microbiol. 2003;35:49-58.
102. Freyer D, Weih M, Weber JR, Burger W, Scholz P, Manz R, Ziegenhorn A, Angestwurm K, Dirnagl U. Pneumococcal cell wall components induce nitric oxide synthase and TNF-alpha in astroglial-enriched cultures. Glia. 1996;16:1-6.
103. Shafer RA, Murphy S. Activated astrocytes induce nitric oxide synthase-2 in cerebral endothelium via tumor necrosis factor alpha. Glia. 1997;21:370-9.
104. Kim S, Moon C, Wie MB, Kim H, Tanuma N, Matsumoto Y, Shin T. Enhanced expression of constitutive and inducible forms of nitric oxide synthase in autoimmune encephalomyelitis. J Vet Sci. 2000;1:11-7.
105. Bourdoulous S, Bensaid A, Martinez D, Sheikboudou C, Trap I, Strosberg AD, Couraud PO. Infection of bovine brain microvessel endothelial cells with Cowdria ruminantium elicits IL-1 beta, -6, and -8 mRNA production and expression of an unusual MHC class II DQ alpha transcript. J Immunol. 1995;154:4032-8.
106. Wong D, Dorovini-Zis K. Expression of vascular cell adhesion molecule-1 (VCAM-1) by human brain microvessel endothelial cells in primary culture. Microvasc Res. 1995;49:325-39.
107. Pekny M, Nilsson M. Astrocyte activation and reactive gliosis. Glia. 2005;50:427-34.
108. Bowman CC, Rasley A, Tranguch SL, Marriott I. Cultured astrocytes express toll-like receptors for bacterial products. Glia. 2003;43:281-91.
109. Bsibsi M, Ravid R, Gveric D, van Noort JM. Broad expression of Toll-like receptors in the human central nervous system. J Neuropathol Exp Neurol. 2002;61:1013-21.
110. Carpentier PA, Begolka WS, Olson JK, Elhofy A, Karpus WJ, Miller SD. Differential activation of astrocytes by innate and adaptive immune stimuli. Glia. 2005;49:360-74.
111. Farina C, Krumbholz M, Giese T, Hartmann G, Aloisi F, Meinl E. Preferential expression and function of Toll-like receptor 3 in human astrocytes. J Neuroimmunol. 2005;159:12-9.
112. Palma JP, Kwon D, Clipstone NA, Kim BS. Infection with Theiler's murine encephalomyelitis virus directly induces proinflammatory cytokines in primary astrocytes via NF-kappaB activation: potential role for the initiation of demyelinating disease. J Virol. 2003;77:6322-31.
113. Edwards JA, Denis F, Talbot PJ. Activation of glial cells by human coronavirus OC43 infection. J Neuroimmunol. 2000;108:73-81.
114. Esen N, Tanga FY, DeLeo JA, Kielian T. Toll-like receptor 2 (TLR2) mediates astrocyte activation in response to the Gram-positive bacterium Staphylococcus aureus. J Neurochem. 2004;88:746-58.
115. Galea E, Reis DJ, Feinstein DL. Cloning and expression of inducible nitric oxide synthase from rat astrocytes. J Neurosci Res. 1994;37:406-14.
116. Lee SC, Dickson DW, Liu W, Brosnan CF. Induction of nitric oxide synthase activity in human astrocytes by interleukin-1 beta and interferon-gamma. J Neuroimmunol. 1993;46:19-24.
117. Chao CC, Hu S, Ehrlich L, Peterson PK. Interleukin-1 and tumor necrosis factor-alpha synergistically mediate neurotoxicity: involvement of nitric oxide and of N-methyl-D-aspartate receptors. Brain Behav Immun. 1995;9:355-65.
118. Oleszak EL, Katsetos CD, Kuzmak J, Varadhachary A. Inducible nitric oxide synthase in Theiler's murine encephalomyelitis virus infection. J Virol. 1997;71:3228-35.
119. Sun N, Grzybicki D, Castro RF, Murphy S, Perlman S. Activation of astrocytes in the spinal cord of mice chronically infected with a neurotropic coronavirus. Virol. 1995;213:482-93.
120. Zhao ML, Kim MO, Morgello S, Lee SC. Expression of inducible nitric oxide synthase, interleukin-1 and caspase-1 in HIV-1 encephalitis. J Neuroimmunol. 2001;115:182-91.
121. Liu JS, Zhao ML, Brosnan CF, Lee SC. Expression of inducible nitric oxide synthase and nitrotyrosine in multiple sclerosis lesions. Am J Pathol. 2001;158:2057-66.
122. Tran EH, Hardin-Pouzet H, Verge G, Owens T. Astrocytes and microglia express inducible nitric oxide synthase in mice with experimental allergic encephalomyelitis. J Neuroimmunol. 1997;74:121-9.
123. Bagasra O, Michaels FH, Zheng YM, Bobroski LE, Spitsin SV, Fu ZF, Tawadros R, Koprowski H. Activation of the inducible form of nitric oxide synthase in the brains of patients with multiple sclerosis. Proc Natl Acad Sci U S A. 1995;92:12041-5.
124. Okuda Y, Nakatsuji Y, Fujimura H, Esumi H, Ogura T, Yanagihara T, Sakoda S. Expression of the inducible isoform of nitric oxide synthase in the central nervous system of mice correlates with the severity of actively induced experimental allergic encephalomyelitis. J Neuroimmunol. 1995;62:103-12.
125. Barna M, Komatsu T, Reiss CS. Activation of type III nitric oxide synthase in astrocytes following a neurotropic viral infection. Virology. 1996;223:331-43.
126. de Groot CJ, Ruuls SR, Theeuwes JW, Dijkstra CD, van der Valk P. Immunocytochemical characterization of the expression of inducible and constitutive isoforms of nitric oxide synthase in demyelinating multiple sclerosis lesions. J Neuropathol Exp Neurol. 1997;56:10-20.
127. Benveniste EN, Sparacio SM, Norris JG, Grenett HE, Fuller GM. Induction and regulation of interleukin-6 gene expression in rat astrocytes. J Neuroimmunol. 1990;30:201-12.
128. Lee SC, Liu W, Dickson DW, Brosnan CF, Berman JW. Cytokine production by human fetal microglia and astrocytes. Differential induction by lipopolysaccharide and IL-1 beta. J Immunol. 1993;150:2659-67.
129. Lee S, Hong J, Choi SY, Oh SB, Park K, Kim JS, Karin M, Lee SJ. CpG oligodeoxynucleotides induce expression of proinflammatory cytokines and chemokines in astrocytes: the role of c-Jun N-terminal kinase in CpG ODN-mediated NF-kappaB activation. J Neuroimmunol. 2004;153:50-63.
130. Sharif SF, Hariri RJ, Chang VA, Barie PS, Wang RS, Ghajar JB. Human astrocyte production of tumour necrosis factor-alpha, interleukin-1 beta, and interleukin-6 following exposure to lipopolysaccharide endotoxin. Neurol Res. 1993;15:109-12.
131. Takeshita S, Takeshita F, Haddad DE, Janabi N, Klinman DM. Activation of microglia and astrocytes by CpG oligodeoxynucleotides. Neuroreport. 2001;12:3029-32.
132. Maimone D, Guazzi GC, Annunziata P. IL-6 detection in multiple sclerosis brain. J Neurol Sci. 1997;146:59-65.
133. de Vries HE, Blom-Roosemalen MC, van Oosten M, de Boer AG, van Berkel TJ, Breimer DD, Kuiper J. The influence of cytokines on the integrity of the blood-brain barrier in vitro. J Neuroimmunol. 1996;64:37-43.
134. Kaur C, Hao AJ, Wu CH, Ling EA. Origin of microglia. Microsc Res Tech. 2001;54:2-9.
135. Hickey WF, Kimura H. Perivascular microglial cells of the CNS are bone marrow-derived and present antigen in vivo. Science. 1988;239:290-2.
136. Lassmann H, Schmied M, Vass K, Hickey WF. Bone marrow derived elements and resident microglia in brain inflammation. Glia. 1993;7:19-24.
137. Carson MJ. Microglia as liaisons between the immune and central nervous systems: functional implications for multiple sclerosis. Glia. 2002;40:218-31.
138. Aloisi F. Immune function of microglia. Glia. 2001;36:165-79.
139. Olson JK, Miller SD. Microglia initiate central nervous system innate and adaptive immune responses through multiple TLRs. J Immunol. 2004;173:3916-24.
140. Laflamme N, Soucy G, Rivest S. Circulating cell wall components derived from gram-negative, not gram-positive, bacteria cause a profound induction of the gene-encoding Toll-like receptor 2 in the CNS. J Neurochem. 2001;79:648-57.
141. Kielian T, Esen N, Bearden ED. Toll-like receptor 2 (TLR2) is pivotal for recognition of S. aureus peptidoglycan but not intact bacteria by microglia. Glia. 2005;49:567-76.
142. Kielian T, Mayes P, Kielian M. Characterization of microglial responses to Staphylococcus aureus: effects on cytokine, costimulatory molecule, and Toll-like receptor expression. J Neuroimmunol. 2002;130:86-99.
143. Chao CC, Hu S, Sheng WS, Bu D, Bukrinsky MI, Peterson PK. Cytokine-stimulated astrocytes damage human neurons via a nitric oxide mechanism. Glia. 1996;16:276-84.
144. Van Kooten C, Gerritsma JS, Paape ME, van Es LA, Banchereau J, Daha MR. Possible role for CD40-CD40L in the regulation of interstitial infiltration in the kidney. Kidney Int. 1997;51:711-21.
145. Boje KM, Arora PK. Microglial-produced nitric oxide and reactive nitrogen oxides mediate neuronal cell death. Brain Res. 1992;587:250-6.
146. Ebert S, Gerber J, Bader S, Muhlhauser F, Brechtel K, Mitchell TJ, Nau R. Dose-dependent activation of microglial cells by Toll-like receptor agonists alone and in combination. J Neuroimmunol. 2005;159:87-96.
147. Rostasy K, Monti L, Yiannoutsos C, Kneissl M, Bell J, Kemper TL, Hedreen JC, Navia BA. Human immunodeficiency virus infection, inducible nitric oxide synthase expression, and microglial activation: pathogenetic relationship to the acquired immunodeficiency syndrome dementia complex. Ann Neurol. 1999;46:207-16.
148. Boven LA, Gomes L, Hery C, Gray F, Verhoef J, Portegies P, Tardieu M, Nottet HS. Increased peroxynitrite activity in AIDS dementia complex: implications for the neuropathogenesis of HIV-1 infection. J Immunol. 1999;162:4319-27.
149. Mack CL, Neville KL, Miller SD. Microglia are activated to become competent antigen presenting and effector cells in the inflammatory environment of the Theiler's virus model of multiple sclerosis. J Neuroimmunol. 2003;144:68-79.
150. Olson JK, Girvin AM, Miller SD. Direct activation of innate and antigen presenting functions of microglia following infection with Theiler's virus. J Virol. 2001;75:9780-9.
151. Jung DY, Lee H, Jung BY, Ock J, Lee MS, Lee WH, Suk K. TLR4, but not TLR2, signals auto-regulatory apoptosis of cultured microglia: a critical role of IFN-beta as a decision maker. J Immunol. 2005;174:6467-76.
152. Lin X, Njenga MK, Johnson AJ, Pavelko KD, David CS, Pease LR, Rodriguez M. Transgenic expression of Theiler's murine encephalomyelitis virus genes in H-2(b) mice inhibits resistance to virus-induced demyelination. J Virol. 2002;76:7799-811.
153. Suzumura A, Sawada M, Takayanagi T. Production of interleukin-12 and expression of its receptors by murine microglia. Brain Res. 1998;787:139-42.
154. Dalpke AH, Schafer MK, Frey M, Zimmermann S, Tebbe J, Weihe E, Heeg K. Immunostimulatory CpG-DNA activates murine microglia. J Immunol. 2002;168:4854-63.
155. Lehnardt S, Lachance C, Patrizi S, Lefebvre S, Follett PL, Jensen FE, Rosenberg PA, Volpe JJ, Vartanian T. The toll-like receptor TLR4 is necessary for lipopolysaccharide-induced oligodendrocyte injury in the CNS. J Neurosci. 2002;22:2478-86.
156. Iliev AI, Stringaris AK, Nau R, Neumann H. Neuronal injury mediated via stimulation of microglial toll-like receptor-9 (TLR9). FASEB J. 2004;18:412-4.
157. Merrill JE, Ignarro LJ, Sherman MP, Melinek J, Lane TE. Microglial cell cytotoxicity of oligodendrocytes is mediated through nitric oxide. J Immunol. 1993;151:2132-41.
158. Lehnardt S, Massillon L, Follett P, Jensen FE, Ratan R, Rosenberg PA, Volpe JJ, Vartanian T. Activation of innate immunity in the CNS triggers neurodegeneration through a Toll-like receptor 4-dependent pathway. Proc Natl Acad Sci U S A. 2003;100:8514-9.
159. Jones LL, Banati RB, Graeber MB, Bonfanti L, Raivich G, Kreutzberg GW. Population control of microglia: does apoptosis play a role? J Neurocytol. 1997;26:755-70.
160. Shukaliak JA, Dorovini-Zis K. Expression of the beta-chemokines RANTES and MIP-1 beta by human brain microvessel endothelial cells in primary culture. J Neuropathol Exp Neurol. 2000;59:339-52.
161. Harkness KA, Sussman JD, Davies-Jones GA, Greenwood J, Woodroofe MN. Cytokine regulation of MCP-1 expression in brain and retinal microvascular endothelial cells. J Neuroimmunol. 2003;142:1-9.
162. Salmaggi A, Gelati M, Dufour A, Corsini E, Pagano S, Baccalini R, Ferrero E, Scabini S, Silei V, Ciusani E, De Rossi M. Expression and modulation of IFN-gamma-inducible chemokines (IP-10, Mig, and I-TAC) in human brain endothelium and astrocytes: possible relevance for the immune invasion of the central nervous system and the pathogenesis of multiple sclerosis. J Interferon Cytokine Res. 2002;22:631-40.
163. McManus C, Berman JW, Brett FM, Staunton H, Farrell M, Brosnan CF. MCP-1, MCP-2 and MCP-3 expression in multiple sclerosis lesions - an immunohistochemical and in situ hybridization study. J Neuroimmunol. 1998;86:20-9.
164. Sanders VJ, Pittman CA, White MG, Wang G, Wiley CA, Achim CL. Chemokines and receptors in HIV encephalitis. AIDS. 1998;12:1021-6.
165. Simpson JE, Newcombe J, Cuzner ML, Woodroofe MN. Expression of the interferon-gamma-inducible chemokines IP-10 and Mig and their receptor, CXCR3, in multiple sclerosis lesions. Neuropathol Appl Neurobiol. 2000;26:133-42.
166. Ambrosini E, Aloisi F. Chemokines and glial cells: a complex network in the central nervous system. Neurochem Res. 2004;29:1017-38.
167. Sun D, Hu X, Liu X, Whitaker JN, Walker WS. Expression of chemokine genes in rat glial cells: the effect of myelin basic protein-reactive encephalitogenic T cells. J Neurosci Res. 1997;48:192-200.
168. Hua LL, Lee SC. Distinct patterns of stimulus-inducible chemokine mRNA accumulation in human fetal astrocytes and microglia. Glia. 2000;30:74-81.
169. Guo H, Jin YX, Ishikawa M, Huang YM, van der Meide PH, Link H, Xiao BG. Regulation of beta-chemokine mRNA expression in adult rat astrocytes by lipopolysaccharide, proinflammatory and immunoregulatory cytokines. Scand J Immunol. 1998;48:502-8.
170. Palma JP, Kim BS. The scope and activation mechanisms of chemokine gene expression in primary astrocytes following infection with Theiler's virus. J Neuroimmunol. 2004;149:121-9.
171. Palma JP, Kim BS. Induction of selected chemokines in glial cells infected with Theiler's virus. J Neuroimmunol. 2001;117:166-70.
172. Balashov KE, Rottman JB, Weiner HL, Hancock WW. CCR5(+) and CXCR3(+) T cells are increased in multiple sclerosis and their ligands MIP-1alpha and IP-10 are expressed in demyelinating brain lesions. Proc Natl Acad Sci U S A. 1999;96:6873-8.
173. Miyagishi R, Kikuchi S, Takayama C, Inoue Y, Tashiro K. Identification of cell types producing RANTES, MIP-1 alpha and MIP-1 beta in rat experimental autoimmune encephalomyelitis by in situ hybridization. J Neuroimmunol. 1997;77:17-26.
174. Ransohoff RM, Hamilton TA, Tani M, Stoler MH, Shick HE, Major JA, Estes ML, Thomas DM, Tuohy VK. Astrocyte expression of mRNA encoding cytokines IP-10 and JE/MCP-1 in experimental autoimmune encephalomyelitis. FASEB J. 1993;7:592-600.
175. Simpson JE, Newcombe J, Cuzner ML, Woodroofe MN. Expression of monocyte chemoattractant protein-1 and other beta-chemokines by resident glia and inflammatory cells in multiple sclerosis lesions. J Neuroimmunol. 1998;84:238-49.
176. Conant K, Garzino-Demo A, Nath A, McArthur JC, Halliday W, Power C, Gallo RC, Major EO. Induction of monocyte chemoattractant protein-1 in HIV-1 Tat-stimulated astrocytes and elevation in AIDS dementia. Proc Natl Acad Sci U S A. 1998;95:3117-21.
177. Lane TE, Liu MT, Chen BP, Asensio VC, Samawi RM, Paoletti AD, Campbell IL, Kunkel SL, Fox HS, Buchmeier MJ. A central role for CD4(+) T cells and RANTES in virus-induced central nervous system inflammation and demyelination. J Virol. 2000;74:1415-24.
178. Liu MT, Keirstead HS, Lane TE. Neutralization of the chemokine CXCL10 reduces inflammatory cell invasion and demyelination and improves neurological function in a viral model of multiple sclerosis. J Immunol. 2001;167:4091-7.
179. Karpus WJ, Lukacs NW, McRae BL, Streiter RM, Kunkel SL, Miller SD. An important role for the chemokine macrophage inflammatory protein-1 alpha in the pathogenesis of the T cell-mediated autoimmune disease, experimental autoimmune encephalomyelitis. J Immunol. 1995;155:5003-10.
180. Fife BT, Kennedy KJ, Paniagua MC, Lukacs NW, Kunkel SL, Luster AD, Karpus WJ. CXCL10 (IFN-gamma-inducible protein-10) control of encephalitogenic CD4+ T cell accumulation in the central nervous system during experimental autoimmune encephalomyelitis. J Immunol. 2001;166:7617-24.
181. Matsui M, Weaver J, Proudfoot AE, Wujek JR, Wei T, Richer E, Trapp BD, Rao A, Ransohoff RM. Treatment of experimental autoimmune encephalomyelitis with the chemokine receptor antagonist Met-RANTES. J Neuroimmunol. 2002;128:16-22.
182. Klein RS, Izikson L, Means T, Gibson HD, Lin E, Sobel RA, Weiner HL, Luster AD. IFN-inducible protein 10/CXC chemokine ligand 10-independent induction of experimental autoimmune encephalomyelitis. J Immunol. 2004;172:550-9.
183. Tran EH, Kuziel WA, Owens T. Induction of experimental autoimmune encephalomyelitis in C57BL/6 mice deficient in either the chemokine macrophage inflammatory protein-1alpha or its CCR5 receptor. Eur J Immunol. 2000;30:1410-5.
184. Gaupp S, Pitt D, Kuziel WA, Cannella B, Raine CS. Experimental autoimmune encephalomyelitis (EAE) in CCR2(-/-) mice: susceptibility in multiple strains. Am J Pathol. 2003;162:139-50.
185. Karpus WJ. Chemokines and central nervous system disorders. J Neurovirol. 2001;7:8.
186. Fife BT, Huffnagle GB, Kuziel WA, Karpus WJ. CC chemokine receptor 2 is critical for induction of experimental autoimmune encephalomyelitis. J Exp Med. 2000;192:899-905.
187. Izikson L, Klein RS, Charo IF, Weiner HL, Luster AD. Resistance to experimental autoimmune encephalomyelitis in mice lacking the CC chemokine receptor (CCR)2. J Exp Med. 2000;192:1075-80.
188. Huang DR, Wang J, Kivisakk P, Rollins BJ, Ransohoff RM. Absence of monocyte chemoattractant protein 1 in mice leads to decreased local macrophage recruitment and antigen-specific T helper cell type 1 immune response in experimental autoimmune encephalomyelitis. J Exp Med. 2001;193:713-26.
189. Chen BP, Kuziel WA, Lane TE. Lack of CCR2 results in increased mortality and impaired leukocyte activation and trafficking following infection of the central nervous system with a neurotropic coronavirus. J Immunol. 2001;167:4585-92.
190. Bennett JL, Elhofy A, Canto MC, Tani M, Ransohoff RM, Karpus WJ. CCL2 transgene expression in the central nervous system directs diffuse infiltration of CD45(high)CD11b(+) monocytes and enhanced Theiler's murine encephalomyelitis virus-induced demyelinating disease. J Neurovirol. 2003;9:623-36.
191. Elhofy A, Wang J, Tani M, Fife BT, Kennedy KJ, Bennett J, Huang D, Ransohoff RM, Karpus WJ. Transgenic expression of CCL2 in the central nervous system prevents experimental autoimmune encephalomyelitis. J Leukoc Biol. 2005;77:229-37.
192. Karpus WJ, Kennedy KJ. MIP-1alpha and MCP-1 differentially regulate acute and relapsing autoimmune encephalomyelitis as well as Th1/Th2 lymphocyte differentiation. J Leukoc Biol. 1997;62:681-7.
193. Cua DJ, Hinton DR, Stohlman SA. Self-antigen-induced Th2 responses in experimental allergic encephalomyelitis (EAE)-resistant mice. Th2-mediated suppression of autoimmune disease. J Immunol. 1995;155:4052-9.
194. Huang D, Wujek J, Kidd G, He TT, Cardona A, Sasse ME, Stein EJ, Kish J, Tani M, Charo IF, Proudfoot AE, Rollins BJ, Handel T, Ransohoff RM. Chronic expression of monocyte chemoattractant protein-1 in the central nervous system causes delayed encephalopathy and impaired microglial function in mice. FASEB J. 2005;19:761-72.
195. Claudio L, Raine CS, Brosnan CF. Evidence of persistent blood-brain barrier abnormalities in chronic-progressive multiple sclerosis. Acta Neuropathol. 1995;90:228-38.
196. Floris S, Blezer EL, Schreibelt G, Dopp E, van der Pol SM, Schadee-Eestermans IL, Nicolay K, Dijkstra CD, de Vries HE. Blood-brain barrier permeability and monocyte infiltration in experimental allergic encephalomyelitis: a quantitative MRI study. Brain. 2004;127:616-27.
197. Jaworowicz DJ Jr, Korytko PJ, Singh LS, Boje KM. Nitric oxide and prostaglandin E2 formation parallels blood-brain barrier disruption in an experimental rat model of bacterial meningitis. Brain Res Bull. 1998;46:541-6.
198. Petito CK, Cash KS. Blood-brain barrier abnormalities in the acquired immunodeficiency syndrome: immunohistochemical localization of serum proteins in postmortem brain. Ann Neurol. 1992;32:658-66.
199. Quagliarello VJ, Long WJ, Scheld WM. Morphologic alterations of the blood-brain barrier with experimental meningitis in the rat. Temporal sequence and role of encapsulation. J Clin Invest. 1986;77:1084-95.
200. Soilu-Hanninen M, Eralinna JP, Hukkanen V, Roytta M, Salmi AA, Salonen R. Semliki Forest virus infects mouse brain endothelial cells and causes blood-brain barrier damage. J Virol. 1994;68:6291-8.
201. Wiley CA, Schrier RD, Nelson JA, Lampert PW, Oldstone MB. Cellular localization of human immunodeficiency virus infection within the brains of acquired immune deficiency syndrome patients. Proc Natl Acad Sci U S A. 1986;83:7089-93.
202. Kim TA, Avraham HK, Koh YH, Jiang S, Park IW, Avraham S. HIV-1 Tat-mediated apoptosis in human brain microvascular endothelial cells. J Immunol. 2003;170:2629-37.
203. Patrick D, Betts J, Frey EA, Prameya R, Dorovini-Zis K, Finlay BB. Haemophilus influenzae lipopolysaccharide disrupts confluent monolayers of bovine brain endothelial cells via a serum-dependent cytotoxic pathway. J Infect Dis. 1992;165:865-72.
204. Shi B, De Girolami U, He J, Wang S, Lorenzo A, Busciglio J, Gabuzda D. Apoptosis induced by HIV-1 infection of the central nervous system. J Clin Invest. 1996;98:1979-90.
205. Girvin AM, Gordon KB, Welsh CJ, Clipstone NA, Miller SD. Differential abilities of central nervous system resident endothelial cells and astrocytes to serve as inducible antigen-presenting cells. Blood. 2002;99:3692-701.
206. Sedgwick JD, Hughes CC, Male DK, MacPhee IA, ter Meulen V. Antigen-specific damage to brain vascular endothelial cells mediated by encephalitogenic and nonencephalitogenic CD4+ T cell lines in vitro. J Immunol. 1990;145:2474-81.
207. Wang Y, Calder VL, Lightman SL, Greenwood J. Antigen presentation by rat brain and retinal endothelial cells. J Neuroimmunol. 1995;61:231-9.
208. Ginis I, Hallenbeck JM, Liu J, Spatz M, Jaiswal R, Shohami E. Tumor necrosis factor and reactive oxygen species cooperative cytotoxicity is mediated via inhibition of NF-kappaB. Mol Med. 2000;6:1028-41.
209. Abbott NJ. Inflammatory mediators and modulation of blood-brain barrier permeability. Cell Mol Neurobiol. 2000;20:131-47.
210. Deli MA, Descamps L, Dehouck MP, Cecchelli R, Joo F, Abraham CS, Torpier G. Exposure of tumor necrosis factor-alpha to luminal membrane of bovine brain capillary endothelial cells cocultured with astrocytes induces a delayed increase of permeability and cytoplasmic stress fiber formation of actin. J Neurosci Res. 1995;41:717-26.
211. Gloor SM, Weber A, Adachi N, Frei K. Interleukin-1 modulates protein tyrosine phosphatase activity and permeability of brain endothelial cells. Biochem Biophys Res Commun. 1997;239:804-9.
212. Huynh HK, Dorovini-Zis K. Effects of interferon-gamma on primary cultures of human brain microvessel endothelial cells. Am J Pathol. 1993;142:1265-78.
213. Megyeri P, Abraham CS, Temesvari P, Kovacs J, Vas T, Speer CP. Recombinant human tumor necrosis factor alpha constricts pial arterioles and increases blood-brain barrier permeability in newborn piglets. Neurosci Lett. 1992;148:137-40.
214. Quagliarello VJ, Wispelwey B, Long WJ Jr, Scheld WM. Recombinant human interleukin-1 induces meningitis and blood-brain barrier injury in the rat. Characterization and comparison with tumor necrosis factor. J Clin Invest. 1991;87:1360-6.
215. Begolka WS, Vanderlugt CL, Rahbe SM, Miller SD. Differential expression of inflammatory cytokines parallels progression of central nervous system pathology in two clinically distinct models of multiple sclerosis. J Immunol. 1998;161:4437-46.
216. Sato S, Reiner SL, Jensen MA, Roos RP. Central nervous system cytokine mRNA expression following Theiler's murine encephalomyelitis virus infection. J Neuroimmunol. 1997;76:213-23.
217. Buster BL, Weintrob AC, Townsend GC, Scheld WM. Potential role of nitric oxide in the pathophysiology of experimental bacterial meningitis in rats. Infect Immun. 1995;63:3835-9.
218. Giovannoni G, Miller RF, Heales SJ, Land JM, Harrison MJ, Thompson EJ. Elevated cerebrospinal fluid and serum nitrate and nitrite levels in patients with central nervous system complications of HIV-1 infection: a correlation with blood-brain-barrier dysfunction. J Neurol Sci. 1998;156:53-8.
219. Koedel U, Bernatowicz A, Paul R, Frei K, Fontana A, Pfister HW. Experimental pneumococcal meningitis: cerebrovascular alterations, brain edema, and meningeal inflammation are linked to the production of nitric oxide. Ann Neurol. 1995;37:313-23.
220. Komatsu T, Ireland DD, Chung N, Dore A, Yoder M, Shoshkes RC. Regulation of the BBB during viral encephalitis: roles of IL-12 and NOS. Nitric Oxide. 1999;3:327-39.
221. Winkler F, Koedel U, Kastenbauer S, Pfister HW. Differential expression of nitric oxide synthases in bacterial meningitis: role of the inducible isoform for blood-brain barrier breakdown. J Infect Dis. 2001;183:1749-59.
222. Staykova M, Maxwell L, Willenborg D. Kinetics and polarization of the membrane expression of cytokine-induced ICAM-1 on rat brain endothelial cells. J Neuropathol Exp Neurol. 2000;59:120-8.
223. Stins MF, Gilles F, Kim KS. Selective expression of adhesion molecules on human brain microvascular endothelial cells. J Neuroimmunol. 1997;76:81-90.
224. Easton AS, Dorovini-Zis K. The kinetics, function, and regulation of P-selectin expressed by human brain microvessel endothelial cells in primary culture. Microvasc Res. 2001;62:335-45.
225. Wong D, Prameya R, Dorovini-Zis K. In vitro adhesion and migration of T lymphocytes across monolayers of human brain microvessel endothelial cells: regulation by ICAM-1, VCAM-1, E-selectin and PECAM-1. J Neuropathol Exp Neurol. 1999;58:138-52.
226. Barten DM, Ruddle NH. Vascular cell adhesion molecule-1 modulation by tumor necrosis factor in experimental allergic encephalomyelitis. J Neuroimmunol. 1994;51:123-33.
227. Engelhardt B, Conley FK, Butcher EC. Cell adhesion molecules on vessels during inflammation in the mouse central nervous system. J Neuroimmunol. 1994;51:199-208.
228. Irani DN, Griffin DE. Regulation of lymphocyte homing into the brain during viral encephalitis at various stages of infection. J Immunol. 1996;156:3850-7.
229. Sasseville VG, Newman WA, Lackner AA, Smith MO, Lausen NC, Beall D, Ringler DJ. Elevated vascular cell adhesion molecule-1 in AIDS encephalitis induced by simian immunodeficiency virus. Am J Pathol. 1992;141:1021-30.
230. Washington R, Burton J, Todd RF, Newman W, Dragovic L, Dore D. Expression of immunologically relevant endothelial cell activation antigens on isolated central nervous system microvessels from patients with multiple sclerosis. Ann Neurol. 1994;35:89-97.
231. Lee SJ, Park JY, Hou J, Benveniste EN. Transcriptional regulation of the intercellular adhesion molecule-1 gene by proinflammatory cytokines in human astrocytes. Glia. 1999;25:21-32.
232. Rosenman SJ, Shrikant P, Dubb L, Benveniste EN, Ransohoff RM. Cytokine-induced expression of vascular cell adhesion molecule-1 (VCAM-1) by astrocytes and astrocytoma cell lines. J Immunol. 1995;154:1888-99.
233. Shrikant P, Chung IY, Ballestas ME, Benveniste EN. Regulation of intercellular adhesion molecule-1 gene expression by tumor necrosis factor-alpha, interleukin-1 beta, and interferon-gamma in astrocytes. J Neuroimmunol. 1994;51:209-20.
234. Seilhean D, Dzia-Lepfoundzou A, Sazdovitch V, Cannella B, Raine CS, Katlama C, Bricaire F, Duyckaerts C, Hauw JJ. Astrocytic adhesion molecules are increased in HIV-1-associated cognitive/ motor complex. Neuropathol Appl Neurobiol. 1997;23:83-92.
235. Woodman SE, Benveniste EN, Nath A, Berman JW. Human immunodeficiency virus type 1 TAT protein induces adhesion molecule expression in astrocytes. J Neurovirol. 1999;5:678-84.
236. Cannella B, Raine CS. The adhesion molecule and cytokine profile of multiple sclerosis lesions. Ann Neurol. 1995;37:424-35.
237. Gimenez MA, Sim JE, Russell JH. TNFR1-dependent VCAM-1 expression by astrocytes exposes the CNS to destructive inflammation. J Neuroimmunol. 2004;151:116-25.
238. Lee SJ, Benveniste EN. Adhesion molecule expression and regulation on cells of the central nervous system. J Neuroimmunol. 1999;98:77-88.
239. Leppert D, Lindberg RL, Kappos L, Leib SL. Matrix metalloproteinases: multifunctional effectors of inflammation in multiple sclerosis and bacterial meningitis. Brain Res Brain Res Rev. 2001;36:249-57.
240. Leppert D, Waubant E, Galardy R, Bunnett NW, Hauser SL. T cell gelatinases mediate basement membrane transmigration in vitro. J Immunol. 1995;154:4379-89.
241. Pagenstecher A, Stalder AK, Kincaid CL, Shapiro SD, Campbell IL. Differential expression of matrix metalloproteinase and tissue inhibitor of matrix metalloproteinase genes in the mouse central nervous system in normal and inflammatory states. Am J Pathol. 1998;152:729-41.
242. Zhou J, Marten NW, Bergmann CC, Macklin WB, Hinton DR, Stohlman SA. Expression of matrix metalloproteinases and their tissue inhibitor during viral encephalitis. J Virol. 2005;79:4764-73.
243. Conant K, McArthur JC, Griffin DE, Sjulson L, Wahl LM, Irani DN. Cerebrospinal fluid levels of MMP-2, 7, and 9 are elevated in association with human immunodeficiency virus dementia. Ann Neurol. 1999;46:391-8.
244. Kolb SA, Lahrtz F, Paul R, Leppert D, Nadal D, Pfister HW, Fontana A. Matrix metalloproteinases and tissue inhibitors of metalloproteinases in viral meningitis: upregulation of MMP-9 and TIMP-1 in cerebrospinal fluid. J Neuroimmunol. 1998;84:143-50.
245. Paul R, Lorenzl S, Koedel U, Sporer B, Vogel U, Frosch M, Pfister HW. Matrix metalloproteinases contribute to the blood-brain barrier disruption during bacterial meningitis. Ann Neurol. 1998;44:592-600.
246. Maeda A, Sobel RA. Matrix metalloproteinases in the normal human central nervous system, microglial nodules, and multiple sclerosis lesions. J Neuropathol Exp Neurol. 1996;55:300-9.
247. Vos CM, van Haastert ES, de Groot CJ, van der Valk P, de Vries HE. Matrix metalloproteinase-12 is expressed in phagocytotic macrophages in active multiple sclerosis lesions. J Neuroimmunol. 2003;138:106-14.
248. Cossins JA, Clements JM, Ford J, Miller KM, Pigott R, Vos W, van der Valk P, de Groot CJ. Enhanced expression of MMP-7 and MMP-9 in demyelinating multiple sclerosis lesions. Acta Neuropathol (Berl). 1997;94:590-8.
249. Gijbels K, Galardy RE, Steinman L. Reversal of experimental autoimmune encephalomyelitis with a hydroxamate inhibitor of matrix metalloproteases. J Clin Invest. 1994;94:2177-82.
250. Keogh B, Sheahan BJ, Atkins GJ, Mills KH. Inhibition of matrix metalloproteinases ameliorates blood-brain barrier disruption and neuropathological lesions caused by avirulent Semliki Forest virus infection. Vet Immunol Immunopathol. 2003;94:185-90.
251. Kwok LY, Miletic H, Lutjen S, Soltek S, Deckert M, Schluter D. Protective immunosurveillance of the central nervous system by Listeria-specific CD4 and CD8 T cells in systemic listeriosis in the absence of intracerebral Listeria. J Immunol. 2002;169:2010-9.
252. Griffin DE. Immune responses to RNA-virus infections of the CNS. Nat Rev Immunol. 2003;3:493-502.
253. Goverman J, Perchellet A, Huseby ES. The role of CD8(+) T cells in multiple sclerosis and its animal models. Curr Drug Targets Inflamm Allergy. 2005;4:239-45.
254. Cross AH, Trotter JL, Lyons J. B cells and antibodies in CNS demyelinating disease. J Neuroimmunol. 2001;112:1-14.
255. Ponomarev ED, Dittel BN. Gamma delta T cells regulate the extent and duration of inflammation in the central nervous system by a Fas ligand-dependent mechanism. J Immunol. 2005;174:4678-87.
256. Tompkins SM, Padilla J, Dal Canto MC, Ting JP, Van Kaer L, Miller SD. De novo central nervous system processing of myelin antigen is required for the initiation of experimental autoimmune encephalomyelitis. J Immunol. 2002;168:4173-83.
257. Sedgwick JD, Mason DW. The mechanism of inhibition of experimental allergic encephalomyelitis in the rat by monoclonal antibody against CD4. J Neuroimmunol. 1986;13:217-32.
258. McDevitt HO, Perry R, Steinman LA. Monoclonal anti-Ia antibody therapy in animal models of autoimmune disease. Ciba Foundation Symp. 1987;129:184-93.
259. Ben-Nun A, Wekerle H, Cohen IR. The rapid isolation of clonable antigen-specific T lymphocyte lines capable of mediating autoimmune encephalomyelitis. Eur J Immunol. 1981;11:195-9.
260. Trotter J, Sriram S, Rassenti L, Chou CH, Fritz RB, Steinman L. Characterization of T cell lines and clones from SJL/J and (BALB/c x SJL/J)F1 mice specific for myelin basic protein. J Immunol. 1985;134:2322-7.
261. Zamvil S, Nelson P, Trotter J, Mitchell D, Knobler R, Fritz R, Steinman L. T-cell clones specific for myelin basic protein induce chronic relapsing paralysis and demyelination. Nature. 1985;317:355-8.
262. Schluesener HJ, Wekerle H. Autoaggressive T lymphocyte lines recognizing the encephalitogenic region of myelin basic protein: in vitro selection from unprimed rat T lymphocyte populations. J Immunol. 1985;135:3128-33.
263. Ando DG, Clayton J, Kono D, Urban JL, Sercarz EE. Encephalitogenic T cells in the B10.PL model of experimental allergic encephalomyelitis (EAE) are of the Th-1 lymphokine subtype. Cell Immunol. 1989;124:132-43.
264. Kuchroo VK, Martin CA, Greer JM, Ju ST, Sobel RA, Dorf ME. Cytokines and adhesion molecules contribute to the ability of myelin proteolipid protein-specific T cell clones to mediate experimental autoimmune encephalomyelitis. J Immunol. 1993;151:4371-82.
265. Baron JL, Madri JA, Ruddle NH, Hashim G, Janeway CA. Surface expression of alpha 4 integrin by CD4 T cells is required for their entry into brain parenchyma. J Exp Med. 1993;177:57-68.
266. Cua DJ, Hinton DR, Stohlman SA. Self-antigen-induced Th2 responses in experimental allergic encephalomyelitis (EAE)-resistant mice. Th2-mediated suppression of autoimmune disease. J Immunol. 1995;155:4052-9.
267. Lafaille JJ, Van de Keere F, Hsu AL, Baron JL, Haas W, Raine CS, Tonegawa S. Myelin basic protein-specific T helper 2 (Th2) cells cause experimental autoimmune encephalomyelitis in immunodeficient hosts rather than protect them from the disease. J Exp Med. 1997;186:307-12.
268. Lassmann H, Ransohoff RM. The CD4-Th1 model for multiple sclerosis: a critical [correction of crucial] re-appraisal. Trends Immunol. 2004;25:132-7.
269. Sospedra M, Martin R. Immunology of multiple sclerosis. Annu Rev Immunol. 2005;23:683-747.
270. Krogsgaard M, Wucherpfennig KW, Canella B, Hansen BE, Svejgaard A, Pyrdol J, Ditzel H, Raine C, Engberg J, Fugger L. Visualization of myelin basic protein (MBP) T cell epitopes in multiple sclerosis lesions using a monoclonal antibody specific for the human histocompatibility leukocyte antigen (HLA)-DR2-MBP 85-99 complex. J Exp Med. 2000;191:1395-412.
271. Ota K, Matsui M, Milford EL, Mackin GA, Weiner HL, Hafler DA. T-cell recognition of an immunodominant myelin basic protein epitope in multiple sclerosis. Nature. 1990;346:183-7.
272. Allegretta M, Nicklas JA, Sriram S, Albertini RJ. T cells responsive to myelin basic protein in patients with multiple sclerosis. Science. 1990;247:718-21.
273. Oksenberg JR, Panzara MA, Begovich AB, Mitchell D, Erlich HA, Murray RS, Shimonkevitz R, Sherritt M, Rothbard J, Bernard CC. Selection for T-cell receptor V beta-D beta-J beta gene rearrangements with specificity for a myelin basic protein peptide in brain lesions of multiple sclerosis. Nature. 1993;362:68-70.
274. Bielekova B, Goodwin B, Richert N, Cortese I, Kondo T, Afshar G, Gran B, Eaton J, Antel J, Frank JA, McFarland HF, Martin R. Encephalitogenic potential of the myelin basic protein peptide (amino acids 83-99) in multiple sclerosis: results of a phase II clinical trial with an altered peptide ligand. Nat Med. 2000;6:1167-75.
275. Madsen LS, Andersson EC, Jansson L, Krogsgaard M, Andersen CB, Engberg J, Strominger JL, Svejgaard A, Hjorth JP, Holmdahl R, Wucherpfennig KW, Fugger L. A humanized model for multiple sclerosis using HLA-DR2 and a human T-cell receptor. Nat Genet. 1999;23:343-7.
276. Archambault AS, Sim J, Gimenez MA, Russell JH. Defining antigen-dependent stages of T cell migration from the blood to the central nervous system parenchyma. Eur J Immunol. 2005;35:1076-85.
277. McCarron RM, Fallis RJ, McFarlin DE. Alterations in T cell antigen specificity and class II restriction during the course of chronic relapsing experimental allergic encephalomyelitis. J Neuroimmunol. 1990;29:73-9.
278. Perry LL, Barzaga-Gilbert E, Trotter JL. T cell sensitization to proteolipid protein in myelin basic protein-induced experimental allergic encephalomyelitis. J Neuroimmunol. 1991;33:7-16.
279. Lehmann PV, Forsthuber T, Miller A, Sercarz EE. Spreading of T-cell autoimmunity to cryptic determinants of an autoantigen. Nature. 1992;358:155-7.
280. Jansson L, Diener P, Engstrom A, Olsson T, Holmdahl R. Spreading of the immune response to different myelin basic protein peptides in chronic experimental autoimmune encephalomyelitis in B10.RIII mice. Eur J Immunol. 1995;25:2195-200.
281. Cross AH, Tuohy VK, Raine CS. Development of reactivity to new myelin antigens during chronic relapsing autoimmune demyelination. Cell Immunol. 1993;146:261-9.
282. McRae BL, Vanderlugt CL, Dal Canto MC, Miller SD. Functional evidence for epitope spreading in the relapsing pathology of experimental autoimmune encephalomyelitis. J Exp Med. 1995;182:75-85.
283. Vanderlugt CL, Eagar TN, Neville KL, Nikcevich KM, Bluestone JA, Miller SD. Pathologic role and temporal appearance of newly emerging autoepitopes in relapsing experimental autoimmune encephalomyelitis. J Immunol. 2000;164:670-8.
284. Yu M, Johnson JM, Tuohy VK. A predictable sequential determinant spreading cascade invariably accompanies progression of experimental autoimmune encephalomyelitis: a basis for peptide-specific therapy after onset of clinical disease. J Exp Med. 1996;183:1777-88.
285. Voskuhl RR, Farris RW, Nagasato K, McFarland HF, Dalcq MD. Epitope spreading occurs in active but not passive EAE induced by myelin basic protein. J Neuroimmunol. 1996;70:103-11.
286. Targoni OS, Baus J, Hofstetter HH, Hesse MD, Karulin AY, Boehm BO, Forsthuber TG, Lehmann PV. Frequencies of neuroantigen-specific T cells in the central nervous system versus the immune periphery during the course of experimental allergic encephalomyelitis. J Immunol. 2001;166:4757-64.
287. Miller SD, Katz-Levy Y, Neville KL, Vanderlugt CL. Virus-induced autoimmunity: epitope spreading to myelin autoepitopes in Theiler's virus infection of the central nervous system. Adv Virus Res. 2001;56:199-217.
288. Borrow P, Welsh CJ, Tonks P, Dean D, Blakemore WF, Nash AA. Investigation of the role of delayed-type-hypersensitivity responses to myelin in the pathogenesis of Theiler's virus-induced demyelinating disease. Immunology. 1998;93:478-84.
289. Katz-Levy Y, Neville KL, Padilla J, Rahbe SM, Begolka WS, Girvin AM, Olson JK, Vanderlugt CL, Miller SD. Temporal development of autoreactive Th1 responses and endogenous antigen presentation of self myelin epitopes by CNS-resident APCs in Theiler's virus-infected mice. J Immunol. 2000;165:5304-14.
290. Klehmet J, Shive C, Guardia-Wolff R, Petersen I, Spack EG, Boehm BO, Weissert R, Forsthuber TG. T cell epitope spreading to myelin oligodendrocyte glycoprotein in HLA-DR4 transgenic mice during experimental autoimmune encephalomyelitis. Clin Immunol. 2004;111:53-60.
291. Ellmerich S, Takacs K, Mycko M, Waldner H, Wahid F, Boyton RJ, Smith PA, Amor S, Baker D, Hafler DA, Kuchroo VK, Altmann DM. Disease-related epitope spread in a humanized T cell receptor transgenic model of multiple sclerosis. Eur J Immunol. 2004;34:1839-48.
292. Tuohy VK, Yu M, Yin L, Kawczak JA, Kinkel PR. Regression and spreading of self-recognition during the development of autoimmune demyelinating disease. J Autoimmun. 1999;13:11-20.
293. Ristori G, Giubilei F, Giunti D, Perna A, Gasperini C, Buttinelli C, Salvetti M, Uccelli A. Myelin basic protein intramolecular spreading without disease progression in a patient with multiple sclerosis. J Neuroimmunol. 2000;110:240-3.
294. Uccelli A, Ristori G, Giunti D, Seri M, Montesperelli C, Caroli F, Solaro C, Murialdo A, Marchese M, Buttinelli C, Mancardi G, Salvetti M. Dynamics of the reactivity to MBP in multiple sclerosis. J Neurovirol. 2000;6 Suppl 2:S52-S6.
295. Goebels N, Hofstetter H, Schmidt S, Brunner C, Wekerle H, Hohlfeld R. Repertoire dynamics of autoreactive T cells in multiple sclerosis patients and healthy subjects: epitope spreading versus clonal persistence. Brain. 2000;123 Pt 3:508-18.
296. Neville KL, Padilla J, Miller SD. Myelin-specific tolerance attenuates the progression of a virus-induced demyelinating disease: Implications for the treatment of MS. J Neuroimmunol. 2002;123:18-29.
297. Phillips MJ, Needham M, Weller RO. Role of cervical lymph nodes in autoimmune encephalomyelitis in the Lewis rat. J Pathol. 1997;182:457-64.
298. Mohindru M, Kang B, Kim BS. Functional maturation of proteolipid protein(139-151)-specific Th1 cells in the central nervous system in experimental autoimmune encephalomyelitis. J Neuroimmunol. 2004;155:127-35.
299. de Vos AF, van Meurs M, Brok HP, Boven LA, Hintzen RQ, van der Valk P, Ravid R, Rensing S, Boon L, 't Hart BA, Laman JD. Transfer of central nervous system autoantigens and presentation in secondary lymphoid organs. J Immunol. 2002;169:5415-23.
300. Karman J, Ling C, Sandor M, Fabry Z. Initiation of immune responses in brain is promoted by local dendritic cells. J Immunol. 2004;173:2353-61.
301. Carson MJ, Reilly CR, Sutcliffe JG, Lo D. Disproportionate recruitment of CD8+ T cells into the central nervous system by professional antigen-presenting cells. Am J Pathol. 1999;154:481-94.
302. Provencio JJ, Kivisakk P, Tucky BH, Luciano MG, Ransohoff RM. Comparison of ventricular and lumbar cerebrospinal fluid T cells in non-inflammatory neurological disorder (NIND) patients. J Neuroimmunol. 2005;163:179-84.
303. Tipold A, Moore P, Jungi TW, Sager H, Vandevelde M. Lymphocyte subsets and CD45RA positive T-cells in normal canine cerebrospinal fluid. J Neuroimmunol. 1998;82:90-5.
304. Seabrook TJ, Johnston M, Hay JB. Cerebral spinal fluid lymphocytes are part of the normal recirculating lymphocyte pool. J Neuroimmunol. 1998;91:100-7.
305. Krakowski ML, Owens T. Naive T lymphocytes traffic to inflamed central nervous system, but require antigen recognition for activation. Eur J Immunol. 2000;30:1002-9.
306. Bauer J, Bradl M, Hickley WF, Forss-Petter S, Breitschopf H, Linington C, Wekerle H, Lassmann H. T-cell apoptosis in inflammatory brain lesions: destruction of T cells does not depend on antigen recognition [see comments]. Am J Pathol. 1998;153:715-24.
307. Kitze B, Pette M, Rohrbach E, Städt D, Kappos L, Wekerle H. Myelin-specific T lymphocytes in multiple sclerosis patients and healthy individuals. J Neuroimmunol. 1988;20:237.
308. Pette M, Fujita K, Kitze B, Whitaker JN, Albert E, Kappos L, Wekerle H. Myelin basic protein-specific T lymphocyte lines from MS patients and healthy individuals. Neurology. 1990;40:1770-6.
309. Hellings N, Baree M, Verhoeven C, D'Hooghe MB, Medaer R, Bernard CC, Raus J, Stinissen P. T-cell reactivity to multiple myelin antigens in multiple sclerosis patients and healthy controls. J Neurosci Res. 2001;63:290-302.
310. Hoftberger R, Aboul-Enein F, Brueck W, Lucchinetti C, Rodriguez M, Schmidbauer M, Jellinger K, Lassmann H. Expression of major histocompatibility complex class I molecules on the different cell types in multiple sclerosis lesions. Brain Pathol. 2004;14:43-50.
311. Matsumoto Y, Fujiwara M. In situ detection of class I and II major histocompatibility complex antigens in the rat central nervous system during experimental allergic encephalomyelitis. An immunohistochemical study. J Neuroimmunol. 1986;12:265-77.
312. Traugott U. Multiple sclerosis: relevance of class I and class II MHC-expressing cells to lesion development. J Neuroimmunol. 1987;16:283-302.
313. Risau W, Engelhardt B, Wekerle H. Immune function of the blood-brain barrier: incomplete presentation of protein (auto-)antigens by rat brain microvascular endothelium in vitro. J Cell Biol. 1990;110:1757-66.
314. Welsh CJ, Sapatino B, Rosenbaum B, Smith R, Linthicum S. Correlation between susceptibility to demyelination and interferon-gamma induction of major histocompatibility complex class II antigens on murine cerebrovascular endothelial cells. J Neuroimmunol. 1993;48:91-7.
315. Jemison LM, Williams SK, Lublin FD, Knobler RL, Korngold R. Interferon-gamma-inducible endothelial cell class II major histocompatibility complex expression correlates with strain- and site-specific susceptibility to experimental allergic encephalomyelitis. J Neuroimmunol. 1993;47(1):15-22.
316. Omari KI, Dorovini-Zis K. Expression and function of the costimulatory molecules B7-1 (CD80) and B7-2 (CD86) in an in vitro model of the human blood-brain barrier. J Neuroimmunol. 2001;113:129-41.
317. Omari KM, Dorovini-Zis K. CD40 expressed by human brain endothelial cells regulates CD4+ T cell adhesion to endothelium. J Neuroimmunol. 2003;134:166-78.
318. Prat A, Biernacki K, Becher B, Antel JP. B7 expression and antigen presentation by human brain endothelial cells: requirement for proinflammatory cytokines. J Neuropathol Exp Neurol. 2000;59:129-36.
319. + T lymphocytes. J Immunol. 1992;148:1985-92.
320. McCarron RM, Spatz M, Kempski O, Hogan RN, Muehl L, McFarlin DE. Interaction between myelin basic protein-sensitized T lymphocytes and murine cerebral vascular endothelial cells. J Immunol. 1986;137:3428-35.
321. + cells by murine brain microvessel endothelial cells and smooth muscle/pericytes. J Immunol. 1993;151:38-47.
322. Pryce G, Male D, Sedgwick J. Antigen presentation in brain: brain endothelial cells are poor stimulators of T-cell proliferation. Immunology. 1989;66:207-12.
323. Goodall CA, Curtis AS, Lang SC. Modulation of adhesion of lymphocytes to murine brain endothelial cells in vitro: relation to class II major histocompatibility complex expression. J Neuroimmunol. 1992;37:9-22.
324. Traugott U, Raine CS. Multiple sclerosis. Evidence for antigen presentation in situ by endothelial cells and astrocytes. J Neurol Sci. 1985;69:365-70.
325. Sakai K, Tabira T, Endoh M, Steinman L. Ia expression in chronic relapsing experimental allergic encephalomyelitis induced by long-term cultured T cell lines in mice. Lab Invest. 1986;54:345-52.
326. Traugott U. Detailed analysis of early immunopathologic events during lesion formation in acute experimental autoimmune encephalomyelitis. Cell Immunol. 1989;119:114-29.
327. Sobel RA, Blanchette BW, Bhan AK, Colvin RB. The immunopathology of experimental allergic encephalomyelitis. II. Endothelial cell Ia increases prior to inflammatory cell infiltration. J Immunol. 1984;132:2402-7.
328. Vass K, Lassmann H, Wekerle H, Wisniewski HM. The distribution of Ia antigen in the lesions of rat acute experimental allergic encephalomyelitis. Acta Neuropathol. 1986;70:149-60.
329. Fierz W, Endler B, Reske K, Wekerle H, Fontana A. Astrocytes as antigen-presenting cells. I. Induction of Ia antigen expression on astrocytes by T cells via immune interferon and its effect on antigen presentation. J Immunol. 1985;134:3785-93.
330. Nikcevich KM, Gordon KB, Tan L, Hurst SD, Kroepfl JF, Gardinier M, Barrett TA, Miller SD. Interferon-gamma activated primary murine astrocytes express B7 costimulatory molecules and prime naive antigen-specific T cells. J Immunol. 1997;158:614-21.
331. Soos JM, Morrow J, Ashley TA, Szente BE, Bikoff EK, Zamvil SS. Astrocytes express elements of the class II endocytic pathway and process central nervous system autoantigen for presentation to encephalitogenic T cells. J Immunol. 1998;161:5959-66.
332. Tan LJ, Gordon KB, Mueller JP, Matis LA, Miller SD. Presentation of proteolipid protein epitopes and B7-1-dependent activation of encephalitogenic T cells by IFN-gamma-activated SJL/J astrocytes. J Immunol. 1998;160:4271-9.
333. Massa PT, ter Meulen V, Fontana A. Hyper-inducibility of Ia antigen on astrocytes correlates with strain specific susceptibility to experimental autoimmune encephalomyelitis. Proc Natl Acad Sci U S A. 1987;84:4219-23.
334. Borrow P, Nash AA. Susceptibility to Theiler's virus-induced demyelinating disease correlates with astrocyte class II induction and antigen presentation. Immunology. 1992;76:133-9.
335. Massa PT, Dorries R, ter Meulen V. Viral particles induce Ia antigen expression on astrocytes. Nature. 1986;320:543-6.
336. Suzumura A, Lavi E, Weiss SR, Silberberg DH. Coronavirus infection induces H-2 antigen expression on oligodendrocytes and astrocytes. Science. 1986;232:991-3.
337. Rodriguez M, Pierce ML, Howie EA. Immune response gene products (Ia antigens) on glial and endothelial cells in virus-induced demyelination. J Immunol. 1987;138:3438-42.
338. Pope JG, Vanderlugt CL, Lipton HL, Rahbe SM, Miller SD. Characterization of and functional antigen presentation by central nervous system mononuclear cells from mice infected with Theiler's murine encephalomyelitis virus. J Virol. 1998;72:7762-71.
339. Lee SC, Moore GR, Golenwsky G, Raine CS. Multiple sclerosis: a role for astroglia in active demyelination suggested by class II MHC expression and ultrastructural study. J Neuropathol Exp Neurol. 1990;49:122-36.
340. Zeinstra E, Wilczak N, Streefland C, De Keyser J. Astrocytes in chronic active multiple sclerosis plaques express MHC class II molecules. Neuroreport. 2000;11:89-91.
341. Battistini L, Fischer FR, Raine CS, Brosnan CF. CD1b is expressed in multiple sclerosis lesions. J Neuroimmunol. 1996;67:145-51.
342. Abdel-Haq N, Hao HN, Lyman WD. Cytokine regulation of CD40 expression in fetal human astrocyte cultures. J Neuroimmunol. 1999;101:7-14.
343. Issazadeh S, Navikas V, Schaub M, Sayegh M, Khoury S. Kinetics of expression of costimulatory molecules and their ligands in murine relapsing experimental autoimmune encephalomyelitis in vivo. J Immunol. 1998;161:1104-12.
344. Cross AH, Ku G. Astrocytes and central nervous system endothelial cells do not express B7-1 (CD80) or B7-2 (CD86) immunoreactivity during experimental autoimmune encephalomyelitis. J Neuroimmunol. 2000;110:76-82.
345. Zeinstra E, Wilczak N, De Keyser J. Reactive astrocytes in chronic active lesions of multiple sclerosis express co-stimulatory molecules B7-1 and B7-2. J Neuroimmunol. 2003;135:166-71.
346. Windhagen A, Newcombe J, Dangond F, Strand C, Woodroofe MN, Cuzner ML, Hafler DA. Expression of costimulatory molecules B7-1 (CD80), B7-2 (CD80), and interleukin 12 cytokine in multiple sclerosis lesions. J Exp Med. 1995;182:1985-96.
347. Aloisi F, Ria F, Penna G, Adorini L. Microglia are more efficient than astrocytes in antigen processing and in Th1 but not Th2 activation. J Immunol. 1998;160:4671-80.
348. Grau V, Herbst B, van der Meide PH, Steiniger B. Activation of microglial and endothelial cells in the rat brain after treatment with interferon-gamma in vivo. Glia. 1997;19:181-9.
349. Frei K, Siepl C, Groscurth P, Bodmer S, Schwerdel C, Fontana A. Antigen presentation and tumor cytotoxicity by interferon-gamma-treated microglial cells. Eur J Immunol. 1987;17:1271-8.
350. Lassmann H, Vass K, Brunner C, Wisniewski HM. Peripheral nervous system lesions in experimental allergic encephalomyelitis. Ultrastructural distribution of T cells and Ia antigen. Acta Neuropathol. 1986;69:193-204.
351. Ulvestad E, Williams K, Bjerkvig R, Tiekotter K, Antel J, Matre R. Human microglial cells have phenotypic and functional characteristics in common with both macrophages and dendritic antigen-presenting cells. J Leuk Biol. 1994;56:732-40.
352. Schmid CD, Sautkulis LN, Danielson PE, Cooper J, Hasel KW, Hilbush BS, Sutcliffe JG, Carson MJ. Heterogeneous expression of the triggering receptor expressed on myeloid cells-2 on adult murine microglia. J Neurochem. 2002;83:1309-20.
353. Phillips LM, Simon PJ, Lampson LA. Site-specific immune regulation in the brain: differential modulation of major histocompatibility complex (MHC) proteins in brainstem vs. hippocampus. J Comp Neurol. 1999;405:322-33.
354. Ford AL, Goodsall AL, Hickey WF, Sedgwick JD. Normal adult ramified microglia separated from other central nervous system macrophages by flow cytometric sorting. Phenotypic differences defined and direct ex vivo antigen presentation to myelin basic protein-reactive CD4+ T cells compared. J Immunol. 1995;154:4309-21.
355. Gerritse K, Laman JD, Noelle RJ, Aruffo A, Ledbetter JA, Boersma WJ, Claassen E. CD40-CD40 ligand interactions in experimental allergic encephalomyelitis and multiple sclerosis. Proc Natl Acad Sci U S A. 1996;93:2499-504.
356. Katz-Levy Y, Neville KL, Girvin AM, Vanderlugt CL, Pope JG, Tan LJ, Miller SD. Endogenous presentation of self myelin epitopes by CNS-resident APCs in Theiler's virus-infected mice. J Clin Invest. 1999;104:599-610.
357. Carson MJ, Reilly CR, Sutcliffe JG, Lo D. Mature microglia resemble immature antigen-presenting cells. Glia. 1998;22:72-85.
358. Aloisi F, Ria F, Columba-Cabezas S, Hess H, Penna G, Adorini L. Relative efficiency of microglia, astrocytes, dendritic cells and B cells in naive CD4+ T cell priming and Th1/Th2 cell restimulation. Eur J Immunol. 1999;29:2705-14.
359. Juedes AE, Ruddle NH. Resident and infiltrating central nervous system APCs regulate the emergence and resolution of experimental autoimmune encephalomyelitis. J Immunol. 2001;166:5168-75.
360. Schmied M, Breitschopf H, Gold R, Zischler H, Rothe G, Wekerle H, Lassmann H. Apoptosis of T lymphocytes in experimental autoimmune encephalomyelitis. Evidence for programmed cell death as a mechanism to control inflammation in the brain. Am J Pathol. 1993;143:446-52.
361. Matyszak MK, Denis-Donini S, Citterio S, Longhi R, Granucci F, Ricciardi-Castagnoli P. Microglia induce myelin basic protein-specific T cell anergy or T cell activation, according to their state of activation. Eur J Immunol. 1999;29:3063-76.
362. Heppner FL, Greter M, Marino D, Falsig J, Raivich G, Hovelmeyer N, Waisman A, Rulicke T, Prinz M, Priller J, Becher B, Aguzzi A. Experimental autoimmune encephalomyelitis repressed by microglial paralysis. Nat Med. 2005;11:146-52.
363. Ulvestad E, Williams K, Bo L, Trapp B, Antel J, Mork S. HLA class II molecules (HLA-DR, -DP, - DQ) on cells in the human CNS studied in situ and in vitro. Immunology. 1994;82:535-41.
364. Williams K, Bar-Or A, Ulvestad E, Olivier A, Antel JP, Yong VW. Biology of adult human microglia in culture: comparisons with peripheral blood monocytes and astrocytes. J Neuropathol Exp Neurol. 1992;51:538-49.
365. Graeber MB, Streit WJ, Buringer D, Sparks DL, Kreutzberg GW. Ultrastructural location of major histocompatibility complex (MHC) class II positive perivascular cells in histologically normal human brain. J Neuropathol Exp Neurol. 1992;51:303-11.
366. Aloisi F, Ria F, Adorini L. Regulation of T-cell responses by CNS antigen-presenting cells: different roles for microglia and astrocytes. Immunol Today. 2000;21:141-7.
367. Williams K, Ulvestad E, Antel JP. B7/BB-1 antigen expression on adult human microglia studied in vitro and in situ. Eur J Immunol. 1994;24:3031-7.
368. Broadwell RD, Baker BJ, Ebert PS, Hickey WF. Allografts of CNS tissue possess a blood-brain barrier: III. Neuropathological, methodological, and immunological considerations. Microsc Res Tech. 1994;27:471-94.
369. Matyszak MK, Perry VH. Bacillus Calmette-Guerin sequestered in the brain parenchyma escapes immune recognition. J Neuroimmunol. 1998;82:73-80.
370. Hart DN, Fabre JW. Demonstration and characterization of Ia-positive dendritic cells in the interstitial connective tissues of rat heart and other tissues, but not brain. J Exp Med. 1981;154:347-61.
371. McMenamin PG. Distribution and phenotype of dendritic cells and resident tissue macrophages in the dura mater, leptomeninges, and choroid plexus of the rat brain as demonstrated in wholemount preparations. J Comp Neurol. 1999;405:553-62.
372. Matyszak MK, Perry VH. The potential role of dendritic cells in immune-mediated inflammatory diseases in the central nervous system. Neuroscience. 1996;74:599-608.
373. Fischer HG, Reichmann G. Brain dendritic cells and macrophages/microglia in central nervous system inflammation. J Immunol. 2001;166:2717-26.
374. Reichmann G, Schroeter M, Jander S, Fischer HG. Dendritic cells and dendritic-like microglia in focal cortical ischemia of the mouse brain. J Neuroimmunol. 2002;129:125-32.
375. Suter T, Malipiero U, Otten L, Ludewig B, Muelethaler-Mottet A, Mach B, Reith W, Fontana A. Dendritic cells and differential usage of the MHC class II transactivator promoters in the central nervous system in experimental autoimmune encephalitis. Eur J Immunol. 2000;30:794-802.
376. Serafini B, Columba-Cabezas S, Di RF, Aloisi F. Intracerebral recruitment and maturation of dendritic cells in the onset and progression of experimental autoimmune encephalomyelitis. Am J Pathol. 2000;157:1991-2002.
377. Rosicarelli B, Serafini B, Sbriccoli M, Lu M, Cardone F, Pocchiari M, Aloisi F. Migration of dendritic cells into the brain in a mouse model of prion disease. J Neuroimmunol. 2005;165:114-20.
378. Cella M, Engering A, Pinet V, Pieters J, Lanzavecchia A. Inflammatory stimuli induce accumulation of MHC class II complexes on dendritic cells. Nature. 1997;388:782-7.
379. Banchereau J, Steinman RM. Dendritic cells and the control of immunity. Nature. 1998;392:245-52.
380. Behi ME, Dubucquoi S, Lefranc D, Zephir H, De Seze J, Vermersch P, Prin L. New insights into cell responses involved in experimental autoimmune encephalomyelitis and multiple sclerosis. Immunol Lett. 2005;96:11-26.
381. Anjuere F, Martin P, Ferrero I, Fraga ML, Del Hoyo GM, Wright N, Ardavin C. Definition of dendritic cell subpopulations present in the spleen, Peyer's patches, lymph nodes, and skin of the mouse. Blood. 1999;93:590-8.
382. Kamath AT, Pooley J, O'Keeffe MA, Vremec D, Zhan Y, Lew AM, D'Amico A, Wu L, Tough DF, Shortman K. The development, maturation, and turn-over rate of mouse spleen dendritic cell populations. J Immunol. 2000;165:6762-70.
383. Asselin-Paturel C, Boonstra A, Dalod M, Durand I, Yessaad N, Dezutter-Dambuyant C, Vicari A, O'Garra A, Biron C, Briere F, Trinchieri G. Mouse type I IFN-producing cells are immature APCs with plasmacytoid morphology. Nat Immunol. 2001;2:1144-50.
384. Maldonado-Lopez R, De Smedt T, Michel P, Godfroid J, Pajak B, Heirman C, Thielemans K, Leo O, Urbain J, Moser M. CD8alpha+ and CD8alpha- subclasses of dendritic cells direct the development of distinct T helper cells in vivo. J Exp Med. 1999;189:587-92.
385. Hochrein H, Shortman K, Vremec D, Scott B, Hertzog P, O'Keeffe M. Differential production of IL-12, IFN-alpha, and IFN-gamma by mouse dendritic cell subsets. J Immunol. 2001;166:5448-55.
386. Pulendran B, Kumar P, Cutler CW, Mohamadzadeh M, Van DT, Banchereau J. Lipopolysaccharides from distinct pathogens induce different classes of immune responses in vivo. J Immunol. 2001;167:5067-76.
387. Suter T, Biollaz G, Gatto D, Bernasconi L, Herren T, Reith W, Fontana A. The brain as an immune privileged site: dendritic cells of the central nervous system inhibit T cell activation. Eur J Immunol. 2003;33:2998-3006.
388. Fischer HG, Bonifas U, Reichmann G. Phenotype and functions of brain dendritic cells emerging during chronic infection of mice with Toxoplasma gondii. J Immunol. 2000;164:4826-34.
389. Schmied M, Breitschopf H, Gold R, Zischler H, Rothe G, Wekerle H, Lassmann H. Apoptosis of T lymphocytes in experimental autoimmune encephalomyelitis. Evidence for programmed cell death as a mechanism to control inflammation in the brain. Am J Pathol. 1993;143:446-52.
390. Langenkamp A, Messi M, Lanzavecchia A, Sallusto F. Kinetics of dendritic cell activation: impact on priming of TH1, TH2 and nonpolarized T cells. Nat Immunol. 2000;1:311-6.
391. Magliozzi R, Columba-Cabezas S, Serafini B, Aloisi F. Intracerebral expression of CXCL13 and BAFF is accompanied by formation of lymphoid follicle-like structures in the meninges of mice with relapsing experimental autoimmune encephalomyelitis. J Neuroimmunol. 2004;148:11-23.
392. Columba-Cabezas S, Serafini B, Ambrosini E, Aloisi F. Lymphoid chemokines CCL19 and CCL21 are expressed in the central nervous system during experimental autoimmune encephalomyelitis: implications for the maintenance of chronic neuroinflammation. Brain Pathol. 2003;13:38-51.
393. Pashenkov M, Huang YM, Kostulas V, Haglund M, Soderstrom M, Link H. Two subsets of dendritic cells are present in human cerebrospinal fluid. Brain. 2001;124:480-92.
394. Press R, Nennesmo I, Kouwenhoven M, Huang YM, Link H, Pashenkov M. Dendritic cells in the cerebrospinal fluid and peripheral nerves in Guillain-Barre syndrome and chronic inflammatory demyelinating polyradiculoneuropathy. J Neuroimmunol. 2005;159:165-76.
395. Plumb J, Armstrong MA, Duddy M, Mirakhur M, McQuaid S. CD83-positive dendritic cells are present in occasional perivascular cuffs in multiple sclerosis lesions. Mult Scler. 2003;9:142-7.
396. Miller SD, Vanderlugt CL, Lenschow DJ, Pope JG, Karandikar NJ, Dal Canto MC, Bluestone JA. Blockade of CD28/B7-1 interaction prevents epitope spreading and clinical relapses of murine EAE. Immunity. 1995;3:739-45.
397. Karandikar NJ, Vanderlugt CL, Bluestone JA, Miller SD. Targeting the B7/CD28:CTLA-4 costimulatory system in CNS autoimmune disease. J Neuroimmunol. 1998;89:10-8.
398. Lemos MP, Esquivel F, Scott P, Laufer TM. MHC class II expression restricted to CD8alpha+ and CD11b+ dendritic cells is sufficient for control of Leishmania major. J Exp Med. 2004;199:725-30.
399. Bauer J, Huitinga I, Zhao W, Lassmann H, Hickey WF, Dijkstra CD. The role of macrophages, perivascular cells, and microglial cells in the pathogenesis of experimental autoimmune encephalomyelitis. Glia. 1995;15:437-46.
400. Tran EH, Hoekstra K, Van Rooijen N, Dijkstra CD, Owens T. Immune invasion of the central nervous system parenchyma and experimental allergic encephalomyelitis, but not leukocyte extravasation from blood, are prevented in macrophage-depleted mice. J Immunol. 1998;161:3767-75.
401. Becher B, Durell BG, Miga AV, Hickey WF, Noelle RJ. The clinical course of experimental autoimmune encephalomyelitis and inflammation is controlled by the expression of CD40 within the central nervous system. J Exp Med. 2001;193:967-74.
402. Becher B, Durell BG, Noelle RJ. Experimental autoimmune encephalitis and inflammation in the absence of interleukin-12. J Clin Invest. 2002;110:493-7.
403. Gran B, Zhang GX, Yu S, Li J, Chen XH, Ventura ES, Kamoun M, Rostami A. IL-12p35-deficient mice are susceptible to experimental autoimmune encephalomyelitis: evidence for redundancy in the IL-12 system in the induction of central nervous system autoimmune demyelination. J Immunol. 2002;169:7104-10.
404. Cua DJ, Sherlock J, Chen Y, Murphy CA, Joyce B, Seymour B, Lucian L, To W, Kwan S, Churakova T, Zurawski S, Wiekowski M, Lira SA, Gorman D, Kastelein RA, Sedgwick JD. Interleukin-23 rather than interleukin-12 is the critical cytokine for autoimmune inflammation of the brain. Nature. 2003;421:744-8.
405. Becher B, Durell BG, Noelle RJ. IL-23 produced by CNS-resident cells controls T cell encephalitogenicity during the effector phase of experimental autoimmune encephalomyelitis. J Clin Invest. 2003;112:1186-91.
406. Inaba K, Inaba M, Deguchi M, Hagi K, Yasumizu R, Ikehara S, Muramatsu S, Steinman RM. Granulocytes, macrophages, and dendritic cells arise from a common major histocompatibility complex class II-negative progenitor in mouse bone marrow. Proc Natl Acad Sci U S A. 1993;90:3038-42.
407. Randolph GJ, Inaba K, Robbiani DF, Steinman RM, Muller WA. Differentiation of phagocytic monocytes into lymph node dendritic cells in vivo. Immunity. 1999;11:753-61.
408. Perry VH, Gordon S. Macrophages and microglia in the nervous system. Trends Neurosci. 1988;11:273-7.
409. Sedgwick JD, Schwender S, Imrich H, Dörries R, Butcher GW, ter Meulen V. Isolation and direct characterization of resident microglial cells from the normal and inflamed central nervous system. Proc Natl Acad Sci U S A. 1991;88:7438-42.
410. Santambrogio L, Belyanskaya SL, Fischer FR, Cipriani B, Brosnan CF, Ricciardi-Castagnoli P, Stern LJ, Strominger JL, Riese R. Developmental plasticity of CNS microglia. Proc Natl Acad Sci U S A. 2001;98:6295-300.
411. Fischer HG, Bielinsky AK. Antigen presentation function of brain-derived dendriform cells depends on astrocyte help. Int Immunol. 1999;11:1265-74.
412. Koguchi K, Nakatsuji Y, Okuno T, Sawada M, Sakoda S. Microglial cell cycle-associated proteins control microglial proliferation in vivo and in vitro and are regulated by GM-CSF and density-dependent inhibition. J Neurosci Res. 2003;74:898-905.
413. Kandanearatchi A, Zuckerman M, Smith M, Vyakarnam A, Everall IP. Granulocyte-macrophage colony-stimulating factor enhances viral load in human brain tissue: amelioration with stavudine. AIDS. 2002;16:413-20.
414. Morrissey PJ, Bressler L, Park LS, Alpert A, Gillis S. Granulocyte-macrophage colony-stimulating factor augments the primary antibody response by enhancing the function of antigen-presenting cells. J Immunol. 1987;139:1113-9.
415. Ousman SS, David S. MIP-1alpha, MCP-1, GM-CSF, and TNF-alpha control the immune cell response that mediates rapid phagocytosis of myelin from the adult mouse spinal cord. J Neurosci. 2001;21:4649-56.
416. Chang M, Suen Y, Lee SM, Baly D, Buzby JS, Knoppel E, Wolpe S, Cairo MS. Transforming growth factor-beta 1, macrophage inflammatory prorein-1 alpha, and interleukin-8 gene expression is lower in stimulated human neonatal compared with adult mononuclear cells. Blood. 1994;84:118-24.
417. Si Q, Cosenza M, Zhao ML, Goldstein H, Lee SC. GM-CSF and M-CSF modulate beta-chemokine and HIV-1 expression in microglia. Glia. 2002;39:174-83.
418. Fischer HG, Nitzgen B, Reichmann G, Hadding U. Cytokine responses induced by Toxoplasma gondii in astrocytes and microglial cells. Eur J Immunol. 1997;27:1539-48.
419. Flugel A, Berkowicz T, Ritter T, Labeur M, Jenne DE, Li Z, Ellwart JW, Willem M, Lassmann H, Wekerle H. Migratory activity and functional changes of green fluorescent effector cells before and during experimental autoimmune encephalomyelitis. Immunity. 2001;14:547-60.
420. Tarkowski E, Wallin A, Regland B, Blennow K, Tarkowski A. Local and systemic GM-CSF increase in Alzheimer's disease and vascular dementia. Acta Neurologica Scandinavica. 2001;103:166-74.
421. Lyons JA, Zhao ML, Fritz RB. Pathogenesis of acute passive murine encephalomyelitis I. Importance of host-derived cells as determined by kinetic analysis. J Neuroimmunol. 1998;86:92-103.
422. Medana IM, Gallimore A, Oxenius A, Martinic MM, Wekerle H, Neumann H. MHC class I-restricted killing of neurons by virus-specific CD8+ T lymphocytes is effected through the Fas/FasL, but not the perform pathway. Eur J Immunol. 2000;30:3623-33.
423. Ruijs TC, Freedman MS, Grenier YG, Olivier A, Antel JP. Human oligodendrocytes are susceptible to cytolysis by major histocompatibility complex class I-restricted lymphocytes. J Neuroimmunol. 1990;27:89-97.
424. Gasque P, Singhrao SK, Neal JW, Gotze O, Morgan BP. Expression of the receptor for complement C5a (CD88) is up-regulated on reactive astrocytes, microglia, and endothelial cells in the inflamed human central nervous system. Am J Pathol. 1997;150:31-41.
425. Gasque P, Fontaine M, Morgan BP. Complement expression in human brain - biosynthesis of terminal pathway components and regulators in human glial-cells and cell-lines. J Immunol. 1995;154:4726-33.
426. Gasque P, Morgan BP. Complement regulatory protein expression by a human oligodendrocyte cell line: cytokine regulation and comparison with astrocytes. Immunology. 1996;89:338-47.
427. Wang J, Asensio VC, Campbell IL. Cytokines and chemokines as mediators of protection and injury in the central nervous system assessed in transgenic mice. Curr Top Microbiol Immunol. 2002;265:23-48.
428. Selmaj K, Raine CS. Tumor necrosis factor mediates myelin and oligodendrocyte damage in vitro. Ann Neurol. 1988;23:339-46.
429. Vartanian T, Li Y, Zhao M, Stefansson K. Interferon-gamma-induced oligodendrocyte cell death: implications for the pathogenesis of multiple sclerosis. Mol Med. 1995;1:732-43.
430. Hisahara S, Yuan J, Momoi T, Okano H, Miura M. Caspase-11 mediates oligodendrocyte cell death and pathogenesis of autoimmune-mediated demyelination. J Exp Med. 2001;193:111-22.
431. Pouly S, Becher B, Blain M, Antel JP. Interferon-gamma modulates human oligodendrocyte susceptibility to Fas-mediated apoptosis. J Neuropathol Exp Neurol. 2000;59:280-6.
432. Allan SM, Rothwell NJ. Cytokines and acute neurodegeneration. Nat Rev Neurosci. 2001;2:734-44.
433. Bal-Price A, Brown GC. Inflammatory neurodegeneration mediated by nitric oxide from activated glia-inhibiting neuronal respiration, causing glutamate release and excitotoxicity. J Neurosci. 2001;21:6480-91.
434. Mitrovic B, Ignarro LJ, Vinters HV, Akers MA, Schmid I, Uittenbogaart C, Merrill JE. Nitric oxide induces necrotic but not apoptotic cell death in oligodendrocytes. Neuroscience. 1995;65:531-9.
435. Cross AH, Misko TP, Lin RF, Hickey WF, Trotter JL, Tilton RG. Aminoguanidine, an inhibitor of inducible nitric oxide synthase, ameliorates experimental autoimmune encephalomyelitis in SJL mice. J Clin Invest. 1994;93:2684-90.
436. Rose JW, Hill KE, Wada Y, Kurtz CB, Tsunoda I, Fujinami RS, Cross AH. Nitric oxide synthase inhibitor, aminoguanidine, reduces inflammation and demyelination produced by Theiler's virus infection. J Neuroimmunol. 1998;82-9.
437. Sonnewald U, Qu H, Aschner M. Pharmacology and toxicology of astrocyte-neuron glutamate transport and cycling. J Pharmacol Exp Ther. 2002;301:1-6.
438. Arundine M, Tymianski M. Molecular mechanisms of glutamate-dependent neurodegeneration in ischemia and traumatic brain injury. Cell Mol Life Sci. 2004;61:657-68.
439. Matute C, Alberdi E, Domercq M, Perez-Cerda F, Perez-Samartin A, Sanchez-Gomez MV. The link between excitotoxic oligodendroglial death and demyelinating diseases. Trends Neurosci. 2001;24:224-30.
440. Chao CC, Hu S. Tumor necrosis factor-alpha potentiates glutamate neurotoxicity in human fetal brain cell cultures. Dev Neurosci. 1994;16:172-9.
441. Qiu Z, Sweeney DD, Netzeband JG, Gruol DL. Chronic interleukin-6 alters NMDA receptor-mediated membrane responses and enhances neurotoxicity in developing CNS neurons. J Neurosci. 1998;18:10445-56.
442. Takahashi JL, Giuliani F, Power C, Imai Y, Yong VW. Interleukin-1beta promotes oligodendrocyte death through glutamate excitotoxicity. Ann Neurol. 2003;53:588-95.
443. Fine SM, Angel RA, Perry SW, Epstein LG, Rothstein JD, Dewhurst S, Gelbard HA. Tumor necrosis factor alpha inhibits glutamate uptake by primary human astrocytes. Implications for pathogenesis of HIV-1 dementia. J Biol Chem. 1996;271:15303-6.
444. Piani D, Frei K, Do KQ, Cuenod M, Fontana A. Murine brain macrophages induced NMDA receptor mediated neurotoxicity in vitro by secreting glutamate. Neurosci Lett. 1991;133:159-62.
445. Darman J, Backovic S, Dike S, Maragakis NJ, Krishnan C, Rothstein JD, Irani DN, Kerr DA. Viral-induced spinal motor neuron death is non-cell-autonomous and involves glutamate excitotoxicity. J Neurosci. 2004;24:7566-75.
446. Hardin-Pouzet H, Krakowski M, Bourbonniere L, Didier-Bazes M, Tran E, Owens T. Glutamate metabolism is down-regulated in astrocytes during experimental allergic encephalomyelitis. Glia. 1997;20:79-85.
447. Ohgoh M, Hanada T, Smith T, Hashimoto T, Ueno M, Yamanishi Y, Watanabe M, Nishizawa Y. Altered expression of glutamate transporters in experimental autoimmune encephalomyelitis. J Neuroimmunol. 2002;125:170-8.
448. Nargi-Aizenman JL, Havert MB, Zhang M, Irani DN, Rothstein JD, Griffin DE. Glutamate receptor antagonists protect from virus-induced neural degeneration. Ann Neurol. 2004;55:541-9.
449. Smith T, Groom A, Zhu B, Turski L. Autoimmune encephalomyelitis ameliorated by AMPA antagonists. Nat Med. 2000;6:62-6.
450. Wallstrom E, Diener P, Ljungdahl A, Khademi M, Nilsson CG, Olsson T. Memantine abrogates neurological deficits, but not CNS inflammation, in Lewis rat experimental autoimmune encephalomyelitis. J Neurol Sci. 1996;137:89-96.