Microglia as liaisons between the immune and central nervous systems: Functional implications for multiple sclerosis

GLIA

Volumn 40, Issue 2, 2002, Pages 218-231

  Carson, Monica J ^a  

^a SCRIPPS RESEARCH INSTITUTE   (United States)

Author keywords

Autoimmunity; Microglia; Multiple sclerosis; Pathogenesis

Indexed keywords

ANIMAL; ANTIGEN PRESENTATION; CENTRAL NERVOUS SYSTEM; ENCEPHALITIS; HUMAN; IMMUNE SYSTEM; IMMUNOLOGY; LYMPHOCYTE; MICROGLIA; MULTIPLE SCLEROSIS; MYELIN SHEATH; REVIEW; SIGNAL TRANSDUCTION; T LYMPHOCYTE;

ANIMALS; ANTIGEN PRESENTATION; CENTRAL NERVOUS SYSTEM; ENCEPHALITIS; HUMANS; IMMUNE SYSTEM; LYMPHOCYTES; MICROGLIA; MULTIPLE SCLEROSIS; MYELIN SHEATH; SIGNAL TRANSDUCTION; T-LYMPHOCYTES;

EID: 0036847841     PISSN: 08941491     EISSN: None     Source Type: Journal    
DOI: 10.1002/glia.10145     Document Type: Review

References (112)

1. Aloisi F 2001. Immune function of microglia. Glia 36:165-179.
2. Aloisi F, Penna G, Polazzi E, Minghetti L, Adorini L. 1999. CD40-CD154 interaction and IFN-gamma are required for IL-12 but not prostaglandin E2 secretion by microglia during antigen presentation to Th1 cells. J Immunol 162:1384-1391.
3. Aloisi F, Ria F, Adorini L. 2000a. Regulation of T-cell responses by CNS antigen-presenting cells: Different roles for microglia and astrocytes. Immunol Today 21:141-147.
4. Aloisi F, De Simone R, Columba-Cabezas S, Penna G, Adorini L. 2000b. Functional maturation of adult mouse resting microglia into an APC is promoted by granulocyte-macrophage colony-stimulating factor and interaction with Th1 cells. J Immunol 164:1705-1712.
5. Aschner M, Allen JW, Kimelberg HK, LoPachin RM, Streit WJ, 1999, Glial cells in neurotoxicity development. Annu Rev Pharmacol Toxicol 39:151-173.
6. Aw SE. 1986. Autoimmune disease-Pathogenesis through molecular mimicry at the tripeptide level. Ann Acad Med Singapore 15:546-554.
7. Banati RB, Newcombe J, Gunn RN, Cagnin A, Turkheimer F, Heppner F, Price G, Wegner F, Giovannoni G, Miller DH, Perkin GD, Smith T, Hewson AK, Bydder G, Kreutzberg GW, Jones T, Cuzner ML, Myers R. 2000. The peripheral benzodiazepine binding site in the brain in multiple sclerosis: Quantitative in vivo imaging of microglia as a measure of disease activity. Brain 123(Pt 11):2321-2337.
8. Bauer J, Huitinga I, Zhao W, Lassmann H, Hickey WF, Dijkstra CD. 1995. The role of macrophages, perivascular cells, and microglial cells in the pathogenesis of experimental autoimmune encephalomyelitis. Glia 15:437-446.
9. Bauer J, Rauschka H, Lassmann H. 2001. Inflammation in the nervous system: The human perspective. Glia 36:235-243.
10. Becher B, Antel JP. 1996. Comparison of phenotypic and functional properties of immediately ex vivo and cultured human adult microglia. Glia 18:1-10.
11. Becher B, Fedorowicz V, Antel JP. 1996. Regulation of CD14 expression on human adult central nervous system-derived microglia. J Neurosci Res 45:375-381.
12. Becher B, Prat A, Antel JP. 2000. Brain-immune connection: Immune-regulatory properties of CNS-resident cells. Glia 29:293-304.
13. Bonetti B, Pohl J, Gao YL, Raine CS. 1997. Cell death during autoimmune demyelination: Effector but not target cells are eliminated by apoptosis. J Immunol 159:5733-5741.
14. Brabb T, von Dassow P, Ordonez N, Schnabel B, Duke B, Goverman J. 2000. In situ tolerance within the central nervous system as a mechanism for preventing autoimmunity. J Exp Med 192:871-880.
15. Brex PA, Ciccarelli O, O'Riordan JI, Sailer M, Thompson AJ, Miller DH. 2002. A longitudinal study of abnormalities on MRI and disability from multiple sclerosis. N Engl J Med 346:158-164.
16. Carson MJ, Lo D. 2001. Immunology. The push-me pull-you of T cell activation. Science 293:618-619.
17. Carson MJ, Sutcliffe JG. 2001. The role of microglia in CNS inflammatory disease: Friend or foe? In: Campbell A, editor. Inflammatory Events in Neurodegeneration. Scettsdale, AZ: Prominent Press. p 1-14.
18. Carson MJ, Reilly CR, Sutcliffe JG, Lo D. 1998. Mature microglia resemble immature antigen-presenting cells. Glia 22:72-85.
19. Carson MJ, Sutcliffe JG, Campbell IL. 1999a. Microglia stimulate naive T-cell differentiation without stimulating T-cell proliferation. J Neurosci Res 55:127-134.
20. + T cells into the central nervous system by professional antigen-presenting cells. Am J Pathol 154:481-494.
21. Cash E, Rott O. 1994. Microglial cells qualify as the stimulators of unprimed CD4+ and CD8+ T lymphocytes in the central nervous system. Clin Exp Immunol 98:313-318.
22. Cash E, Zhang Y, Rott O. 1993. Microglia present myelin antigens to T cells after phagocytosis of oligodendrocytes. Cell Immunol 147: 129-138.
23. Chan A, Magnus T, Gold R, 2001. Phagocytosis of apoptotic inflammatory cells by microglia and modulation by different cytokines: Mechanism for removal of apoptotic cells in the inflamed nervous system. Glia 33:87-95.
24. Chen SC, Leach MW, Chen Y, Cai XY, Sullivan L, Wiekowski M, Dovey-Hartman BJ, Zlotnik A, Lira SA. 2002. Central nervous system inflammation and neurological disease in transgenic mice expressing the CC chemokine CCL21 in oligodendrocytes. J Immunol 168:1009-1017.
25. Ciccarelli O, Werring DJ, Wheeler-Kingshott CA, Barker GJ, Parker GJ, Thompson AJ, Miller DH. 2001. Investigation of MS normal-appearing brain using diffusion tensor MRI with clinical correlations. Neurology 56:926-933.
26. Delgado R, Carlin A, Airaghi L, Demitri MT, Meda L, Galimberti D, Baron P, Lipton JM, Catania A. 1998. Melanocortin peptides inhibit production of proinflammatory cytokines and nitric oxide by activated microglia. J Leukoc Biol 63:740-745.
27. De Stefano N, Matthews PM, Fu L, Narayanan S, Stanley J, Francis GS, Antel JP, Arnold DL. 1998. Axonal damage correlates with disability in patients with relapsing-remitting multiple sclerosis. Results of a longitudinal magnetic resonance spectroscopy study. Brain 121(Pt 8):1469-1477.
28. De Stefano N, Narayanan S, Francis GS, Arnaoutelis R, Tartaglia MC, Antel JP, Matthews PM, Arnold DL. 2001. Evidence of axonal damage in the early stages of multiple sclerosis and its relevance to disability. Arch Neurol 58:65-70.
29. Evans CF, Horwitz MS, Hobbs MV, Oldstone MB. 1996. Viral infection of transgenic mice expressing a viral protein in oligodendrocytes leads to chronic central nervous system autoimmune disease. J Exp Med 184:2371-2384.
30. Fan L, Reilly CR, Luo Y, Doff ME, Lo D. 2000. Cutting edge: Ectopic expression of the chemokine TCA4/SLC is sufficient to trigger lymphoid neogenesis. J Immunol 164:3955-3959.
31. Flaris NA, Densmore TL, Molleston MC, Hickey WF. 1993. Characterization of microglia and macrophages in the central nervous system of rats: Definition of the differential expression of molecules using standard and novel monoclonal antibodies in normal CNS and in four models of parenchymal reaction. Glia 7:34-40.
32. Flugel A, Bradl M, Kreutzberg GW, Graeber MB. 2001. Transformation of donor-derived bone marrow precursors into host microglia during autoimmune CNS inflammation and during the retrograde response to axotomy. J Neurosci Res 66:74-82.
33. Ford AL, Goodsall AL, Hickey WF, Sedgwick JD. 1995. 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 154:4309-4321.
34. Ford AL, Foulcher E, Lemckert FA, Sedgwick JD. 1996. Microglia induce CD4 T lymphocyte final effector function and death. J Exp Med 184:1737-1745.
35. Fressinaud C, Vallat JM, Pouplard-Barthelaix A. 1996. Platelet-derived growth factor partly prevents chemically induced oligodendrocyte death and improves myelin-like membranes repair in vitro. Glia 16:40-50.
36. Fujinami RS, Oldstone MB. 1985. Amino acid homology between the encephalitogenic site of myelin basic protein and virus: Mechanism for autoimmunity. Science 230:1043-1045.
37. Gobin SJ, Montagne L, Van Zutphen M, Van Der Valk P, Van Den Elsen PJ, De Groot CJ. 2001. Upregulation of transcription factors controlling MHC expression in multiple sclerosis lesions. Glia 36:68-77.
38. Gran B, Hemmer B, Martin R. 1999. Molecular mimicry and multiple sclerosis-A possible role for degenerate T cell recognition in the induction of autoimmune responses. J Neural Transm 55(suppl):19-31.
39. Hailer NP, Heppner FL, Haas D, Nitsch R. 1997. Fluorescent dye prelabelled microglial cells migrate into organotypic hippocampal slice cultures and ramify. Eur J Neurosci 9:863-866.
40. Hauben E, Butovsky O, Nevo U, Yoles E, Moalem G, Agranov E, Mor F, Leibowitz-Amit R, Pevsner E, Akselrod S, Neeman M, Cohen IR, Schwartz M. 2000. Passive or active immunization with myelin basic protein promotes recovery from spinal cord contusion. J Neurosci 20:6421-6430.
41. Heese K, Hock C, Otten U. 1998. Inflammatory signals induce neurotrophin expression in human microglial cells. J Neurochem 70: 699-707.
42. Hickey WF, Kimura H. 1988. Perivascular microglial cells of the CNS are bone marrow-derived and present antigen in vivo. Science 239: 290-292.
43. Hoek RM, Ruuls SR, Murphy CA, Wright GJ, Goddard R, Zurawski SM, Blom B, Homola ME, Streit WJ, Brown MH, Barclay AN, Sedgwick JD. 2000. Down-regulation of the macrophage lineage through interaction with OX2 (CD200). Science 290:1768-1771.
44. Juedes AE, Ruddle NH. 2001. Resident and infiltrating central nervous system APCs regulate the emergence and resolution of experimental autoimmune encephalomyelitis. J Immunol 166:5168-5175.
45. Kassiotis G, Bauer J, Akassoglou K, Lassmann H, Kollias G, Probert L. 1999. A tumor necrosis factor-induced model of human primary demyelinating diseases develops in immunodeficient mice. Eur J Immunol 29:912-917.
46. Keegan BM, Noseworthy JH. 2002. Multiple sclerosis. Annu Rev Med 53:285-302.
47. Kerschensteiner M, Gallmeier E, Behrens L, Leal VV, Misgeld T, Klinkert WE, Kolbeck R, Hoppe E, Oropeza-Wekerle RL, Bartke I, Stadelmann C, Lassmann H, Wekerle H, Hohlfeld R, 1999. Activated human T cells, B cells, and monocytes produce brain-derived neuretrophic factor in vitro and in inflammatory brain lesions: A neuroprotective role of inflammation? J Exp Med 189:865-870.
48. Kim WK, Kan Y, Ganea D, Hart RP, Gozes I, Jonakait GM. 2000. 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 20:3622-3630.
49. Knight SC, Stagg AJ. 1993. Antigen-presenting cell types. Curr Opin Immunol 5:374-382.
50. Krakowski ML, Owens T. 2000. Naive T lymphocytes traffic to inflamed central nervous system, but require antigen recognition for activation. Eur J Immunol 30:1002-1009.
51. Kreutzberg GW. 1996. Microglia: A sensor for pathological events in the CNS. Trends Neurosci 19:312-318.
52. Lafaille JJ, Keere FV, Hsu AL, Baron JL, Haas W, Raine CS, Tonegawa S. 1997. 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 186:307-312.
53. + T cells and RANTES in virus-induced central nervous system inflammation and demyelination. J Virol 74:1415-1424.
54. Lee R, Kermani P, Teng KK, Hempstead BL. 2001. Regulation of cell survival by secreted proneurotrophins. Science 294:1945-1948.
55. Liblau R, Gautam AM. 2000. HLA, molecular mimicry and multiple sclerosis. Rev Immunogenet 2:95-104.
56. Lo D, Feng LL, Li L, Carson MJ, Crowley M, Pauza M, Nguyen A, Reilly CR. 1999. Integrating innate and adaptive immunity in the whole animal. Immunol Rev 169:225-239.
57. Lucchinetti C, Bruck W, Parisi J, Scheithauer B, Rodriguez M, Lassmann H. 2000. Heterogeneity of multiple sclerosis lesions: Implications for the pathogenesis of demyelination. Ann Neurol 47:707-717.
58. Magnus T, Chan A, Grauer O, Toyka KV, Gold R. 2001. Microglial phagocytosis of apoptotic inflammatory T cells leads to down-regulation of microglial immune activation. J Immunol 167:5004-5010.
59. Marten NW, Stohlman SA, Atkinson RD, Hinton DR, Fleming JO, Bergmann CC. 2000. Contributions of CD8+ T cells and viral spread to demyelinating disease. J Immunol 164:4080-4088.
60. Matsumoto Y, Fujiwara M. 1987. Absence of donor-type major histocompatibility complex class I antigen-bearing microglia in the rat central nervous system of radiation bone marrow chimeras. J Neuroimmunol 17:71-82.
61. Matyszak MK. 1998. Infammation in the CNS: Balance between immunological privilege and immune responses. Prog Neurobiol 56:19-35.
62. Matyszak MK, Denis-Donini S, Citterio S, Longhi R, Granucci F, Ricciardi-Castaguoli P. 1999. Microglia induce myelin basic protein-specific T cell anergy or T cell activation, according to their state of activation. Eur J Immunol 29:3063-3076.
63. McCluskey LP, Lampson LA. 2001. Local immune regulation in the central nervous system by substance P vs. glutamate. J Neuroimmunol 116:136-146.
64. Medzhitov R, Janeway CA, Jr. 1998. Innate immune recognition and control of adaptive immune responses. Semin Immunol 10:351-353.
65. Miller SD, Olson JK, Croxford JL. 2001. Multiple pathways to induction of virus-induced autoimmune demyelination: Lessons from Theiler's virus infection. J Autoimmun 16:219-227.
66. Minghetti L, Polazzi E, Nicolini A, Greco A, Levi G. 1999. Possible role of microglial prostanoids and free radicals in neuroprotection and neurodegeneration. Adv Exp Med Biol 468:109-119.
67. Moalem G, Monsonego A, Shani Y, Cohen IR, Schwartz M. 1999a. Differential T cell response in central and peripheral nerve injury: Connection with immune privilege. FASEB J 13:1207-1217.
68. Moalem G, Leibowitz-Amit R, Yoles E, Mor F, Cohen IR, Schwartz M. 19990. Autoimmune T cells protect neurons from secondary degeneration after central nervous system axotomy. Nat Med 5:49-55.
69. Mosmann TR, Sad S. 1996. The expanding universe of T-coll subsets: Th1, Th2 and more. Immunol Today 17:138-146.
70. Myers KJ, Dougherty JP, Ran Y. 1993. In vivo antigen presentation by both brain parenchymal cells and hematopoietically derived cells during the induction of experimental autoimmune encephalomyelitis. J Immunol 151:2252-2260.
71. Neumann H. 2001. Control of glial immune function by neurons. Glia 36:191-199.
72. Neumann H, Misgeld T, Matsumuro K, Wekerle H. 1998. Neurotrophins inhibit major histecompatibility class II inducibility of microglia: Involvement of the p75 neurotrophin receptor. Proc Natl Acad Sci U S A 95:5779-5784.
73. Nguyen VT, Benveniste EN. 2002. Critical role of TNF-alpha and NF-κB in IFN-gamma-induced CD40 expression in microglia/macrophages. J Biol Chem 277:13796-13803.
74. Nicholas RS, Stevens S, Wing MG, Compston DA. 2002. Microglia-derived IGF-2 prevents TNFalpha induced death of mature oligodendrocytes in vitro. J Neuroimmunol 124:36-44.
75. Noseworthy JH. 1999. Progress in determining the causes and treatment of multiple sclerosis. Nature 399(6738)(suppl):A40-A47.
76. Olson JK, Girvin AM, Miller SD. 2001a. Direct activation of innate and antigen-presenting functions of microglia following infection with Theiler's virus. J Virol 75:9780-9789.
77. Olson JK, Croxford JL, Calenoff MA, Dal Canto MC, Miller SD. 2001b. A virus-induced molecular mimicry model of multiple sclerosis. J Clin Invest 108:311-318.
78. Pedersen EB, McNulty JA, Castro AJ, Fox LM, Zimmer J, Finsen B. 1997. Enriched immune-environment of blood-brain barrier deficient areas of normal adult rats. J Neuroimmunol 76:117-131.
79. Pender MP, Rist MJ. 2001. Apoptosis of inflammatory cells in immune control of the nervous system: Role of glia. Glia 36:137-144.
80. Perry VH. 1998. A revised view of the central nervous system micro-environment and major histocompatibility complex class II antigen presentation. J Neuroimmunol 90:113-121.
81. Ploix C, Lo D, Carson MJ. 2001. A ligand for the chemokine receptor CCR7 can influence the homeostatic proliferation of CD4 T cells and progression of autoimmunity. J Immunol 167:6724-6730.
82. Priller J, Flugel A, Wehner T, Boentert M, Haas CA, Prinz M, Fernandez-Klett F, Prass K, Bechmann I, de Boer BA, Frotscher M, Kreutzberg GW, Persons DA, Dirnagl U. 2001. Targeting gene-modified hematopoietic cells to the central nervous system: Use of green fluorescent protein uncovers microglial engraftment. Nat Med 7:1356-1361.
83. Prineas JW, Kwon EE, Cho ES, Sharer LR, Barnett MH, Oleszak EL, Hoffman B, Morgan BP. 2001. Immunopathology of secondary-progressive multiple sclerosis. Ann Neural 50:646-657.
84. Raivich G, Jones LL, Kloss CU, Werner A, Neumann H, Kreutzberg GW. 1998. Immune surveillance in the injured nervous system: T-lymphocytes invade the axotomized mouse facial motor nucleus and aggregate around sites of neuronal degeneration. J Neurosci 18:5804-5816.
85. Ransohoff RM. 1999. Mechanisms of inflammation in MS tissue: Adhesion molecules and chemokines. J Neuroimmunol 98:57-68.
86. Rodriguez M, Miller DJ, Lennon VA. 1996. Immunoglobulin reactive with myelin basic protein promotes CNS remyelination. Neurology 46:538-545.
87. Santambrogio L, Belyanskaya SL, Fischer FR, Cipriani B, Brosnan CF, Ricciardi-Castagnoli P, Stern LJ, Strominger JL, Riese R. 2001. Developmental plasticity of CNS microglia. Proc Natl Acad Sci U S A 98:6295-6300.
88. Schlapbach R, Spanaus KS, Malipiero U, Lens S, Tasinato A, Tschopp J, Fontana A. 2000. TGF-beta induces the expression of the FLICE-inhibitory protein and inhibits Fas-mediated apoptosis of microglia. Eur J Immunol 30:3680-3688.
89. Schmidt S. 1999. Candidate autoantigens in multiple sclerosis. Mult Scler 5:147-160.
90. Schwartz M, Moalem G, Leibowitz Amit R, Cohen IR. 1999. Innate and adaptive immune responses can be beneficial for CNS repair. Trends Neurosci 22:295-299.
91. Scolding N. 2001. The differential diagnosis of multiple sclerosis. J Neurol Neurosurg Psychiatry 71:ii9-15.
92. Scott B, Liblau R, Degermann S, Marconi LA, Ogata L, Caten AJ, McDevitt HO, Lo D. 1994. A role for non-MHC genetic polymorphism in susceptibility to spontaneous auteimmunity. Immunity 1:73-83.
93. Sedgwick JD, Schwender S, Imrich H, Dorries R, Butcher GW, ter Meulen V. 1991. Isolation and direct characterization of resident microglial cells from the normal and inflamed central nervous system. Proc Natl Acad Sci U S A 88:7438-7442.
94. Serpe CJ, Kohm AP, Huppenbauer CB, Sanders VM, Jones KJ. 1999. Exacerbation of facial moteneuron loss after facial nerve transection in severe combined immunodeficient (scid) mice. J Neurosci 19:RC7.
95. Smith ME. 2001. Phagocytic properties of microglia in vitro: Implications for a role in multiple sclerosis and EAE. Microsc Res Tech 54:81-94.
96. Spanaus KS, Schlapbach R, Fontana A. 1998. TNF-alpha and IFN-gamma render microglia sensitive to Fas ligand-induced apoptesis by induction of Fas expression and down-regulation of Bcl-2 and Bcl-xL. Eur J Immunol 28:4398-4408.
97. Sriram S, Rodriguez M. 1997. Indictment of the microglia as the villain in multiple sclerosis. Neurology 48:464-470.
98. Stalder AK, Carson MJ, Pagenstecher A, Asensio VC, Kincaid C, Benedict M, Powell HC, Masliah E, Campbell IL. 1998. Late-onset chronic inflammatory encephalopathy in immune-competent and severe combined immune-deficient (SCID) mice with astrocyte-targeted expression of tumor necrosis factor. Am J Pathol 153:767-783.
99. Stohlman SA, Hinton DR. 2001. Viral induced demyelination. Brain Pathol 11:92-106.
100. Streit WJ. 2000. Microglial response to brain injury: A brief synopsis. Toxicol Pathol 28:28-30.
101. Streit WJ, Walter SA, Pennell NA. 1999. Reactive microgliosis. Prog Neurobiol 57:563-581.
102. Sun D, Hu X, Liu X, Whitaker JN, Walker WS. 1997. Expression of chemokine genes in rat glial cells: The effect of myelin basic protein-reactive encephalitogenic T cells. J Neurosci Res 48:192-200.
103. Tan J, Town T, Saxe M, Paris D, Wu Y, Mullan M. 1999. Ligation of microglial CD40 results in p44/42 mitogen-activated protein kinase-dependent TNF-alpha production that is opposed by TGF-beta 1 and IL-10. J Immunol 163:6614-6621.
104. Tran EH, Hoekstra K, vanRooijen N, Dijkstra CD, Owens T. 1998. 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 161:3767-3775.
105. Trapp BD, Ransohoff RM, Fisher E, Rudick RA. 1999a. Neurodegeneration in multiple sclerosis: Relationship to neurological disability. Neuroscientist 5:48-57.
106. Trapp BD, Bo L, Mork S, Chang A. 19990. Pathogenesis of tissue injury in MS lesions. J Neuroimmunol 98:49-56.
107. Unger ER, Sung JH, Manivel JC, Chenggis ML, Blazar BR, Krivit W 1993. Male donor-derived cells in the brains of female sex-mismatched bone marrow transplant recipients: A Y-chromosome specific in situ hybridization study. J Neuropathol Exp Neurol 52:460-470.
108. Weinshenker BG, Rice GP, Noseworthy JH, Carriere W, Baskerville J, Ebers GC. 1991. The natural history of multiple sclerosis: A geographically based study. 4. Applications to planning and interpretation of clinical therapeutic trials. Brain 114:1057-1067.
109. Wekerle H. 1997. CD4 effector cells in autoimmune diseases of the central nervous system. In: Keane RW, Hickey WF, editors. Immunology of the Nervous System. Oxford: Oxford University Press. p 460-492.
110. Willenborg DO, Staykova MA, Cowden WB. 1999. Our shifting understanding of the role of nitric oxide in autoimmune encephalomyelitis: A review. J Neuroimmunol 100:21-35.
111. Wingerchuk DM, Weinshenker BG. 2000. Multiple sclerosis: Epidemiology, genetics, classification, natural history and clinical outcome measures. Neuroimaging Clin North Am 10:611-624.
112. Wolf SA, Gimsa U, Bechmann I, Nitsch R. 2001. Differential expression of costimulatory molecules B7-1 and B7-2 on microglial cells induced by Th1 and Th2 cells in organotypic brain tissue. Glia 36:414-420.