The ambivalent nature of T-cell infiltration in the central nervous system of patients with multiple sclerosis

Critical Reviews in Immunology

Volumn 27, Issue 1, 2007, Pages 1-13

  Vanderlocht, Joris ^a   Hellings, Niels ^a   Hendriks, Jerome J A ^a   Stinissen, Piet ^a  

^a HASSELT UNIVERSITY   (Belgium)

Author keywords

Multiple sclerosis; Neuroprotection; Neurotrophic factors; Protective autoimmunity

Indexed keywords

GLIAL CELL LINE DERIVED NEUROTROPHIC FACTOR; MYELIN PROTEIN; NEUROKININ; NEUROTROPHIN; T LYMPHOCYTE RECEPTOR ALPHA CHAIN; T LYMPHOCYTE RECEPTOR BETA CHAIN;

ALLERGIC ENCEPHALOMYELITIS; ANTIGEN EXPRESSION; ANTIGEN PRESENTATION; AUTOIMMUNE DISEASE; AUTOIMMUNITY; CD4+ T LYMPHOCYTE; CYTOKINE PRODUCTION; HUMAN; IMMUNOCOMPETENT CELL; IMMUNOPATHOGENESIS; IMMUNOREGULATION; IMMUNOSURVEILLANCE; INFLAMMATION; MULTIPLE SCLEROSIS; NERVE INJURY; NEUROPROTECTION; NEUROTOXICITY; NONHUMAN; PATHOPHYSIOLOGY; PRIORITY JOURNAL; PROTEIN FUNCTION; PROTEIN PROTEIN INTERACTION; REGULATORY T LYMPHOCYTE; REVIEW; T LYMPHOCYTE; TISSUE INJURY;

ANTIGEN PRESENTATION; AUTOIMMUNITY; BRAIN; CELL MOVEMENT; HUMANS; LEUKEMIA INHIBITORY FACTOR; MULTIPLE SCLEROSIS; NERVE GROWTH FACTORS; T-LYMPHOCYTES;

EID: 34247531858     PISSN: 10408401     EISSN: None     Source Type: Journal    
DOI: None     Document Type: Review

References (122)

1. Kornek B, Storch MK, Weissert R, Wallstroem E, Stefferl A, Olsson T, Linington C, Schmidbauer M, Lassmann H. Multiple sclerosis and chronic autoimmune encephalomyelitis: a comparative quantitative study of axonal injury in active, inactive, and remyelinated lesions. Am J Pathol. 2000;157(1):267-76.
2. Kuhlmann T, Lingfeld G, Bitsch A, Schuchardt J, Bruck W. Acute axonal damage in multiple sclerosis is most extensive in early disease stages and decreases over time. Brain. 2002;125:2202-12.
3. Ferguson B, Matyszak MK, Esiri MM, Perry VH. Axonal damage in acute multiple sclerosis lesions. Brain. 1997;120(Pt 3):393-9.
4. Al Omaishi J, Bashir R, Gendelman HE. The cellular immunology of multiple sclerosis. J Leukoc Biol. 1999;65(4):444-52.
5. Piehl F, Lidman O. Neuroinflammation in the rat - CNS cells and their role in the regulation of immune reactions. Immunol Rev. 2001;184:212-25.
6. Becher B, Prat A, Antel JP. Brain-immune connection: immuno-regulatory properties of CNS-resident cells. Glia. 2000;29(4):293-304.
7. Kelly MA, Cavan DA, Penny MA, Mijovic CH, Jenkins D, Morrissey S, Miller DH, Barnett AH, Francis DA. The influence of HLA-DR and -DQ alleles on progression to multiple sclerosis following a clinically isolated syndrome. Hum Immunol. 1993;37(3):185-91.
8. 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(6280):183-7.
9. Zamvil SS, Steinman L. The T lymphocyte in experimental allergic encephalomyelitis. Annu Rev Immunol. 1990;8:579-621.
10. Martin R, McFarland HF, McFarlin DE. Immunological aspects of demyelinating diseases. Annu Rev Immunol. 1992;10:153-87.
11. 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(6035):355-8.
12. Hellings N, Raus J, Stinissen P. Insights into the immunopathogenesis of multiple sclerosis. Immunol Res. 2002;25(1):27-51.
13. 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(3):973-84.
14. 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(6415):68-70.
15. Wucherpfennig KW, Sette A, Southwood S, Oseroff C, Matsui M, Strominger JL, Hafler DA. Structural requirements for binding of an immunodominant myelin basic protein peptide to DR2 isotypes and for its recognition by human T cell clones. J Exp Med. 1994;179(1):279-90.
16. Chou YK, Vainiene M, Whitham R, Bourdette D, Chou CH, Hashim G, Offner H, Vandenbark AA. Response of human T lymphocyte lines to myelin basic protein: association of dominant epitopes with HLA class II restriction molecules. J Neurosci Res. 1989;23(2):207-16.
17. Martin R, Howell MD, Jaraquemada D, Flerlage M, Richert J, Brostoff S, Long EO, McFarlin DE, McFarland HF. A myelin basic protein peptide is recognized by cytotoxic T cells in the context of four HLA-DR types associated with multiple sclerosis. J Exp Med. 1991;173(1):19-24.
18. Venken K, Hellings N, Hensen K, Rummens JL, Medaer R, D'hooghe MB, Dubois W, Raus J, Stinissen P. Secondary progressive in contrast to relapsing-remitting multiple sclerosis patients show a normal CD4(+) CD25(+) regulatory T-cell function and FOXP3 expression. J Neurosci Res. 2006;83(8):1432-46.
19. Viglietta V, Baecher-Allan C, Weiner HL, Hafler DA. Loss of functional suppression by CD4(+) CD25(+) regulatory T cells in patients with multiple sclerosis. J Exp Med. 2004;199(7):971-9.
20. Hellings N, Gelin G, Medaer R, Bruckers L, Palmers Y, Raus J, Stinissen P. Longitudinal study of antimyelin T-cell reactivity in relapsing-remitting multiple sclerosis: association with clinical and MRI activity. J Neuroimmunol. 2002;126(1-2):143-60.
21. Vandevyver C, Mertens N, Vandenelsen P, Medaer R, Raus J, Zhang JW. Clonal expansion of myelin basic protein-reactive T-cells in patients with multiplesclerosis - restricted T-cell receptor-V gene rearrangements and Cdr3 sequence. Eur J Immunol. 1995;25(4):958-68.
22. Hafler DA, Weiner HL. In vivo labeling of blood T cells: rapid traffic into cerebrospinal fluid in multiple sclerosis. Ann Neurol. 1987;22(1):89-93.
23. 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(6):3785-93.
24. Carson MJ, Reilly CR, Sutcliffe JG, Lo D. Mature microglia resemble immature antigen-presenting cells. Glia. 1998;22(1):72-85.
25. Hickey WF, Kimura H. Perivascular microglial cells of the CNS are bone marrow-derived and present antigen in vivo. Science. 1988;239(4837):290-2.
26. Becher B, Antel JP. Comparison of phenotypic and functional properties of immediately ex vivo and cultured human adult microglia. Glia. 1996;18(1):1-10.
27. 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(3):328-34.
28. Hartung HP, Jung S, Stoll G, Zielasek J, Schmidt B, Archelos JJ, Toyka KV. Inflammatory mediators in demyelinating disorders of the CNS and PNS. J Neuroimmunol. 1992;40(2-3):197-210.
29. Buntinx M, Stinissen P, Steels P, Ameloot M, Raus J. Immune-mediated oligodendrocyte injury in multiple sclerosis: molecular mechanisms and therapeutic interventions. Crit Rev Immunol. 2002;22(5-6):391-424.
30. Bergsteindottir K, Brennan A, Jessen KR, Mirsky R. In the presence of dexamethasone, gamma interferon induces rat oligodendrocytes to express major histocompatibility complex class II molecules. Proc Natl Acad Sci U S A. 1992;89(19):9054-8.
31. Horwitz MS, Evans CF, Klier FG, Oldstone MB. Detailed in vivo analysis of interferon-gamma induced major histocompatibility complex expression in the the central nervous system: astrocytes fail to express major histocompatibility complex class I and II molecules. Lab Invest. 1999;79(2):235-42.
32. Lee SC, Raine CS. Multiple sclerosis: oligodendrocytes in active lesions do not express class II major histocompatibility complex molecules. J Neuroimmunol. 1989;25(2-3):261-6.
33. Antel JP, McCrea E, Ladiwala U, Qin YF, Becher B. Non-MHC-restricted cell-mediated lysis of human oligodendrocytes in vitro: Relation with CD56 expression. J Immunol. 1998;160(4):1606-11.
34. Kim SU, Sato Y, Silberberg DH, Pleasure DE, Rorke LB. Long-term culture of human oligodendrocytes. Isolation, growth and identification. J Neurol Sci. 1983;62(1-3):295-301.
35. Grenier Y, Ruijs TC, Robitaille Y, Olivier A, Antel JP. Immunohistochemical studies of adult human glial cells. J Neuroimmunol. 1989;21(2-3):103-15.
36. Neumann H. Molecular mechanisms of axonal damage in inflammatory central nervous system diseases. Curr Opin Neurol. 2003;16(3):267-73.
37. Johnson AJ, Upshaw J, Pavelko KD, Rodriguez M, Pease LR. Preservation of motor function by inhibition of CD8+ virus peptide-specific T cells in Theiler's virus infection. FASEB J. 2001;15(14):2760-2.
38. Medana I, Martinic MA, Wekerle H, Neumann H. Transection of major histocompatibility complex class I-induced neurites by cytotoxic T lymphocytes. Am J Pathol. 2001;159(3):809-15.
39. 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(2-3):89-97.
40. Jurewicz A, Biddison WE, Antel JP. MHC class I-restricted lysis of human oligodendrocytes by myelin basic protein peptide-specific CD8 T lymphocytes. J Immunol. 1998;160(6):3056-9.
41. Russell JH, Ley TJ. Lymphocyte-mediated cytotoxicity. Annu Rev Immunol. 2002;20:323-70.
42. Giuliani F, Goodyer CG, Antel JP, Yong VW. Vulnerability of human neurons to T cell-mediated cytotoxicity. J Immunol. 2003;171(1):368-79.
43. Yong VW. Prospects for neuroprotection in multiple sclerosis. Front Biosci. 2004;9:864-72.
44. Wucherpfennig KW, Newcombe J, Li H, Keddy C, Cuzner ML, Hafler DA. T cell receptor V alpha-V beta repertoire and cytokine gene expression in active multiple sclerosis lesions. J Exp Med. 1992;175(4):993-1002.
45. Stinissen P, Vandevyver C, Medaer R, vandeGaer L, Nies J, Tuyls L, Hafler DA, Raus J, Zhang J. Increased frequency of gamma delta T cells in cerebrospinal fluid and peripheral blood of patients with multiple sclerosis. Reactivity, cytotoxicity, and T cell receptor V gene rearrangements. J Immunol. 1995;154(9):4883-94.
46. Nick S, Pileri P, Tongiani S, Uematsu Y, Kappos L, De Libero G. T cell receptor gamma delta repertoire is skewed in cerebrospinal fluid of multiple sclerosis patients: molecular and functional analyses of antigen-reactive gamma delta clones. Eur J Immunol. 1995;25(2):355-63.
47. Zeine R, Pon R, Ladiwala U, Antel JP, Filion LG, Freedman MS. Mechanism of gamma delta T cell-induced human oligodendrocyte cytotoxicity: relevance to multiple sclerosis. J Neuroimmunol. 1998;87(1-2):49-61.
48. Freedman MS, D'Souza S, Antel JP. gamma delta T-cell-human glial cell interactions. I. In vitro induction of gammadelta T-cell expansion by human glial cells. J Neuroimmunol. 1997;74(1-2):135-42.
49. Burns J, Rosenzweig A, Zweiman B, Lisak RP. Isolation of myelin basic protein-reactive T-cell lines from normal human blood. Cell Immunol. 1983;81(2):435-40.
50. 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(10):1133-6.
51. Wang WZ, Olsson T, Kostulas V, Hojeberg B, Ekre HP, Link H. Myelin antigen reactive T cells in cerebrovascular diseases. Clin Exp Immunol. 1992;88(1):157-62.
52. Olsson T, Sun JB, Solders G, Xiao BG, Hojeberg B, Ekre HP, Link H. Autoreactive T-cell and B-cell responses to myelin antigens after diagnostic Sural Nerve Biopsy. J Neurol Sci. 1993;117(1-2):130-9.
53. Yoles E, Zalish M, Lavie V, Duvdevani R, Ben Bassat S, Schwartz M. GM1 reduces injury-induced metabolic deficits and degeneration in the rat optic nerve. Invest Ophthalmol Vis Sci. 1992;33(13):3586-91.
54. Yoles E, Muller S, Schwartz M. NMDA-receptor antagonist protects neurons from secondary degeneration after partial optic nerve crush. J Neurotrauma. 1997;14(9):665-75.
55. Faden AI. Experimental neurobiology of central nervous system trauma. Crit Rev Neurobiol. 1993;7(3-4):175-86.
56. Moalem G, Leibowitz-Amit R, Yoles E, Mor F, Cohen IR, Schwartz M. Autoimmune T cells protect neurons from secondary degeneration after central nervous system axotomy. Nat Med. 1999;5(1):49-55.
57. 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. Passive or active immunization with myelin basic protein promotes recovery from spinal cord contusion. J Neurosci. 2000;20(17):6421-30.
58. Hofstetter HH, Sewell DL, Liu F, Sandor M, Forsthuber T, Lehmann PV, Fabry Z. Autoreactive T cells promote post-traumatic healing in the central nervous system. J Neuroimmunol. 2003;134(1-2):25-34.
59. Frenkel D, Huang Z, Maron R, Koldzic DN, Moskowitz MA, Weiner HL. Neuroprotection by IL-10-producing MOG CD4+ T cells following ischemic stroke. J Neurol Sci. 2005;233(1-2):125-32.
60. Schwartz M, Kipnis J. Protective autoimmunity: regulation and prospects for vaccination after brain and spinal cord injuries. Trends Mol Med. 2001;7(6):252-8.
61. Yoles E, Hauben E, Palgi O, Agranov E, Gothilf A, Cohen A, Kuchroo V, Cohen IR, Weiner H, Schwartz M. Protective autoimmunity is a physiological response to CNS trauma. J Neurosci. 2001;21(11):3740-8.
62. Schwartz M, Kipnis J. Multiple sclerosis as a byproduct of the failure to sustain protective autoimmunity: a paradigm shift. Neuroscientist. 2002;8(5):405-13.
63. Cohen IR, Schwartz M. Autoimmune maintenance and neuroprotection of the central nervous system. J Neuroimmunol. 1999;100(1-2):111-4.
64. Liu D, Yang R, Yan X, McAdoo DJ. Hydroxyl radicals generated in vivo kill neurons in the rat spinal cord: electrophysiological, histological, and neurochemical results. J Neurochem. 1994;62(1):37-44.
65. Lynch DR, Dawson TM. Secondary mechanisms in neuronal trauma. Curr Opin Neurol. 1994;7(6):510-6.
66. Agrawal SK, Fehlings MG. Mechanisms of secondary injury to spinal cord axons in vitro: role of Na+, Na(+)-K(+)-ATPase, the Na(+)-H+ exchanger, and the Na(+)-Ca2+ exchanger. J Neurosci. 1996;16(2):545-52.
67. Schwab ME, Bartholdi D. Degeneration and regeneration of axons in the lesioned spinal cord. Physiol Rev. 1996;76(2):319-70.
68. Yarom Y, Naparstek Y, Lev-Ram V, Holoshitz J, Ben Nun A, Cohen IR. Immunospecific inhibition of nerve conduction by T lymphocytes reactive to basic protein of myelin. Nature. 1983;303(5914):246-7.
69. Shaked I, Porat Z, Gersner R, Kipnis J, Schwartz M. Early activation of microglia as antigen-presenting cells correlates with T cell-mediated protection and repair of the injured central nervous system. J Neuroimmunol. 2004;146(1-2):84-93.
70. Lewin GR, Barde YA. Physiology of the neurotrophins. Annu Rev Neurosci. 1996;19:289-317.
71. Huang EJ, Reichardt LF. Neurotrophins: roles in neuronal development and function. Annu Rev Neurosci. 2001;24:677-736.
72. Kerschensteiner M, Stadelmann C, Dechant G, Wekerle H, Hohlfeld R. Neurotrophic cross-talk between the nervous and immune systems: implications for neurological diseases. Ann Neurol. 2003;53(3):292-304.
73. Dechant G, Barde YA. The neurotrophin receptor p75(NTR): novel functions and implications for diseases of the nervous system. Nat Neurosci. 2002;5(11):1131-6.
74. Bothwell M. Functional interactions of neurotrophins and neurotrophin receptors. Annu Rev Neurosci. 1995;18:223-53.
75. Segal RA, Greenberg ME. Intracellular signaling pathways activated by neurotrophic factors. Annu Rev Neurosci. 1996;19:463-89.
76. Hohlfeld R, Kerschensteiner M, Stadelmann C, Lassmann H, Wekerle H. The neuroprotective effect of inflammation: implications for the therapy of multiple sclerosis. J Neuroimmunol. 2000;107(2):161-6.
77. Flugel A, Matsumuro K, Neumann H, Klinkert WE, Birnbacher R, Lassmann H, Otten U, Wekerle H. Anti-inflammatory activity of nerve growth factor in experimental autoimmune encephalomyelitis: inhibition of monocyte transendothelial migration. Eur J Immunol. 2001;31(1):11-22.
78. 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(10):5779-84.
79. Villoslada P, Hauser SL, Bartke I, Unger J, Heald N, Rosenberg D, Cheung SW, Mobley WC, Fisher S, Genain CP. Human nerve growth factor protects common marmosets against autoimmune encephalomyelitis by switching the balance of T helper cell type 1 and 2 cytokines within the central nervous system. J Exp Med. 2000;191(10):1799-806.
80. Seidah NG, Benjannet S, Pareek S, Chretien M, Murphy RA. Cellular processing of the neurotrophin precursors of NT3 and BDNF by the mammalian proprotein convertases. FEBS Lett. 1996;379(3):247-50.
81. Lee R, Kermani P, Teng KK, Hempstead BL. Regulation of cell survival by secreted proneurotrophins. Science. 2001;294(5548):1945-8.
82. Chen ZY, Patel PD, Sant G, Meng CX, Teng KK, Hempstead BL, Lee FS. Variant brain-derived neurotrophic factor (BDNF) (Met66) alters the intracellular trafficking and activity-dependent secretion of wild-type BDNF in neurosecretory cells and cortical neurons. J Neurosci. 2004;24(18):4401-11.
83. Lou H, Kim SK, Zaitsev E, Snell CR, Lu B, Loh YP. Sorting and activity-dependent secretion of BDNF require interaction of a specific motif with the sorting receptor carboxypeptidase e. Neuron. 2005;45(2):245-55.
84. Mowla SJ, Pareek S, Farhadi HF, Petrecca K, Fawcett JP, Seidah NG, Morris SJ, Sossin WS, Murphy RA. Differential sorting of nerve growth factor and brain-derived neurotrophic factor in hippocampal neurons. J Neurosci. 1999;19(6):2069-80.
85. Lu B, Pang PT, Woo NH. The yin and yang of neurotrophin action. Nat Rev Neurosci. 2005;6(8):603-14.
86. Ehrhard PB, Erb P, Graumann U, Otten U. Expression of nerve growth factor and nerve growth factor receptor tyrosine kinase Trk in activated CD4-positive T-cell clones. Proc Natl Acad Sci U S A. 1993;90(23):10984-8.
87. Melamed I, Turner CE, Aktories K, Kaplan DR, Gelfand EW. Nerve growth factor triggers microfilament assembly and paxillin phosphorylation in human B lymphocytes. J Exp Med. 1995;181(3):1071-9.
88. Barouch R, Schwartz M. Autoreactive T cells induce neurotrophin production by immune and neural cells in injured rat optic nerve: implications for protective autoimmunity. FASEB J. 2002;16(10):1304-6.
89. Kerschensteiner M, Gallmeier E, Behrens L, Leal VV, Misgeld T, Klinkert WEF, Kolbeck R, Hoppe E, Oropeza-Wekerle RL, Bartke I, Stadelmann C, Lassmann H, Wekerle H, Hohlfeld R. Activated human T cells, B cells, and monocytes produce brain-derived neurotrophic factor in vitro and in inflammatory brain lesions: A neuroprotective role of inflammation? J Exp Med. 1999;189(5):865-70.
90. Moalem G, Gdalyahu A, Shani Y, Otten U, Lazarovici P, Cohen IR, Schwartz M. Production of neurotrophins by activated T cells: implications for neuroprotective autoimmunity. J Autoimmun. 2000;15(3):331-45.
91. Hammarberg H, Lidman O, Lundberg C, Eltayeb SY, Gielen AW, Muhallab S, Svenningsson A, Linda H, Der Meide PH, Cullheim S, Olsson T, Piehl F. Neuroprotection by encephalomyelitis: rescue of mechanically injured neurons and neurotrophin production by CNS-infiltrating T and natural killer cells. J Neurosci. 2000;20(14):5283-91.
92. Baloh RH, Enomoto H, Johnson EM, Jr., Milbrandt J. The GDNF family ligands and receptors - implications for neural development. Curr Opin Neurobiol. 2000;10(1):103-10.
93. Mitsumoto H, Tsuzaka K. Neurotrophic factors and neuro-muscular disease: II. GDNF, other neurotrophic factors, and future directions. Muscle Nerve. 1999;22(8):1000-21.
94. Vargas-Leal V, Bruno R, Derfuss T, Krumbholz M, Hohlfeld R, Meinl E. Expression and function of glial cell line-derived neurotrophic factor family ligands and their receptors on human immune cells. J Immunol. 2005;175(4):2301-8.
95. Gearing DP, Thut CJ, VandeBos T, Gimpel SD, Delaney PB, King J, Price V, Cosman D, Beckmann MP. Leukemia inhibitory factor receptor is structurally related to the IL-6 signal transducer, gp130. EMBO J. 1991;10(10):2839-48.
96. Nicola NA, Hilton DJ. Leukaemia inhibitory factor and its receptor. In: Le Roith D, Bandy C, editors. Growth factors and cytokines in health and disease. Greenwich: JAI Press, Inc; 1996.
97. Murphy M, Dutton R, Koblar S, Cheema S, Bartlett P. Cytokines which signal through the LIF receptor and their actions in the nervous system. Prog Neurobiol. 1997;52(5):355-78.
98. Vanderlocht J, Hellings N, Hendriks JJ, Vandenabeele F, Moreels M, Buntinx M, Hoekstra D, Antel JP, Stinissen P. Leukemia inhibitory factor is produced by myelin-reactive T cells from multiple sclerosis patients and protects against tumor necrosis factor-alpha-induced oligodendrocyte apoptosis. J Neurosci Res. 2006;83(5):763-74.
99. Vanderlocht J, Hendriks JJ, Venken K, Stinissen P, Hellings N. Effects of IFN-beta, leptin and simvastatin on LIF secretion by T lymphocytes of MS patients and healthy controls. J Neuroimmunol. 2006;177(1-2):189-200.
100. Butzkueven H, Emery B, Cipriani T, Marriott MP, Kilpatrick TJ. Endogenous leukemia inhibitory factor production limits autoimmune demyelination and oligodendrocyte loss. Glia. 2006;53(7):696-703.
101. Butzkueven H, Zhang JG, Soilu-Hanninen M, Hochrein H, Chionh F, Shipham KA, Emery B, Turnley AM, Petratos S, Ernst M, Bartlett PF, Kilpatrick TJ. LIF receptor signaling limits immune-mediated demyelination by enhancing oligodendrocyte survival. Nat Med. 2002;8(6):613-9.
102. Sugiura S, Lahav R, Han J, Kou SY, Banner LR, de Pablo F, Patterson PH. Leukaemia inhibitory factor is required for normal inflammatory responses to injury in the peripheral and central nervous systems in vivo and is chemotactic for macrophages in vitro. Eur J Neurosci. 2000;12(2):457-66.
103. Semkova I, Krieglstein J. Neuroprotection mediated via neurotrophic factors and induction of neurotrophic factors. Brain Res Brain Res Rev. 1999;30(2):176-88.
104. Marzella PL, Gillespie LN, Clark GM, Bartlett PF, Kilpatrick TJ. The neurotrophins act synergistically with LIF and members of the TGF-beta superfamily to promote the survival of spiral ganglia neurons in vitro. Hear Res. 1999;138(1-2):73-80.
105. Wong V, Arriaga R, Ip NY, Lindsay RM. The neurotrophins BDNF, NT-3 and NT-4/5, but not NGF, up-regulate the cholinergic phenotype of developing motor neurons. Eur J Neurosci. 1993;5(5):466-74.
106. Stirling DP, Khodarahmi K, Liu J, McPhail LT, McBride CB, Steeves JD, Ramer MS, Tetzlaff W. Minocycline treatment reduces delayed oligodendrocyte death, attenuates axonal dieback, and improves functional outcome after spinal cord injury. J Neurosci. 2004;24(9):2182-90.
107. Merrill JE, Ignarro LJ, Sherman MP, Melinek J, Lane TE. Microglial cell cytotoxicity of oligodendrocytes is mediated through nitric-oxide. J Immunol. 1993;151(4):2132-41
108. Bieber AJ, Kerr S, Rodriguez M. Efficient central nervous system remyelination requires T cells. Ann Neurol. 2003;53(5):680-4.
109. Jack C, Ruffini F, Bar-Or A, Antel JP. Microglia and multiple sclerosis. J Neurosci Res. 2005;81(3):363-73.
110. Williams K, Alvarez X, Lackner AA. Central nervous system perivascular cells are immunoregulatory cells that connect the CNS with the peripheral immune system. Glia. 2001;36(2):156-64.
111. Kim SU, De Vellis J. Microglia in health and disease. J Neurosci Res. 2005;81(3):302-13.
112. Butovsky O, Ziv Y, Schwartz A, Landa G, Talpalar AE, Pluchino S, Martino G, Schwartz M. Microglia activated by IL-4 or IFN-gamma differentially induce neurogenesis and oligodendrogenesis from adult stem/progenitor cells. Mol Cell Neurosci. 2006;31(1):149-60.
113. Raivich G, Jones LL, Kloss CUA, Werner A, Neumann H, Kreutzberg GW. 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. 1998;18(15):5804-16.
114. Serpe CJ, Kohm AP, Hupperbauer CB, Sanders VM, Jones KJ. Exacerbation of facial motoneuron loss after facial nerve transection in severe combined immunodeficient (scid) mice. J Neurosci. 1999;RC7:1-5.
115. Byram SC, Carson MJ, Deboy CA, Serpe CJ, Sanders VM, Jones KJ. CD4-positive T cell-mediated neuroprotection requires dual compartment antigen presentation. J Neurosci. 2004;24(18):4333-9.
116. Read S, Malmstrom V, Powrie F. Cytotoxic T lymphocyte-associated antigen 4 plays an essential role in the function of CD25(+)CD4(+) regulatory cells that control intestinal inflammation. J Exp Med. 2000;192(2):295-302.
117. Green EA, Gorelik L, McGregor CM, Tran EH, Flavell RA. CD4(+)CD25(+) T regulatory cells control anti-islet CD8(+) T cells through TGF-beta-TGF-beta receptor interactions in type 1 diabetes. Proc Natl Acad Sci U S A. 2003;100(19):10878-83.
118. Kohm AP, Carpentier PA, Anger HA, Miller SD. Cutting edge: CD4(+)CD25(+) regulatory T cells suppress antigen-specific autoreactive immune responses and central nervous system inflammation during active experimental autoimmune encephalomyelitis. J Immunol. 2002;169(9):4712-6.
119. Kipnis J, Mizrahi T, Hauben E, Shaked I, Shevach E, Schwartz M. Neuroprotective autoimmunity: naturally occurring CD4(+)CD25(+) regulatory T cells suppress the ability to withstand injury to the central nervous system. Proc Natl Acad Sci U S A. 2002;99(24):15620-5.
120. Kipnis J, Avidan H, Caspi RR, Schwartz M. Dual effect of CD4(+)CD25(+) regulatory T cells in neurodegeneration: a dialogue with microglia. Proc Natl Acad Sci U S A. 2004;101:14663-9.
121. Kramer R, Zhang Y, Gehrmann J, Gold R, Thoenen H, Wekerle H. Gene transfer through the blood-nerve barrier: NGF-engineered neuritogenic T lymphocytes attenuate experimental autoimmune neuritis. Nat Med. 1995;1(11):1162-6.
122. Flugel A, Willem M, Berkowicz T, Wekerle H. Gene transfer into CD4+ T lymphocytes: green fluorescent protein-engineered, encephalitogenic T cells illuminate brain autoimmune responses. Nat Med. 1999;5(7):843-7.