T-cells in multiple sclerosis

Results and Problems in Cell Differentiation

Volumn 51, Issue , 2010, Pages 75-98

  Severson, Christopher ^a   Hafler, David A ^a  

^a BRIGHAM AND WOMEN S HOSPITAL   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

ALLERGIC ENCEPHALOMYELITIS; ANIMAL; ARTICLE; AUTOIMMUNITY; CENTRAL NERVOUS SYSTEM; HUMAN; IMMUNOLOGY; LYMPHOCYTE ACTIVATION; MOUSE; MULTIPLE SCLEROSIS; PATHOLOGY; REGULATORY T LYMPHOCYTE; T LYMPHOCYTE; T LYMPHOCYTE SUBPOPULATION; EXPERIMENTAL AUTOIMMUNE ENCEPHALOMYELITIS;

ANIMALS; AUTOIMMUNITY; CENTRAL NERVOUS SYSTEM; ENCEPHALOMYELITIS, AUTOIMMUNE, EXPERIMENTAL; HUMANS; LYMPHOCYTE ACTIVATION; MICE; MULTIPLE SCLEROSIS; T-LYMPHOCYTE SUBSETS; T-LYMPHOCYTES; T-LYMPHOCYTES, REGULATORY;

EID: 76949101765     PISSN: 00801844     EISSN: 18610412     Source Type: Book Series    
DOI: 10.1007/400_2009_12     Document Type: Article

References (150)

1. Abbas AK, Murphy KM, et al (1996) Functional diversity of helper T lymphocytes. Nature 383(6603):787-793
2. Aggarwal S, Ghilardi N, et al (2003) Interleukin-23 promotes a distinct CD4 T cell activation state characterized by the production of interleukin-17. J Biol Chem 278(3):1910-1914
3. Anderson AC, Anderson DE, et al (2007) Promotion of tissue inflammation by the immune receptor Tim-3 expressed on innate immune cells. Science 318(5853):1141-1143
4. Anderson DE, Sharpe AH, et al (1999) The B7-CD28/CTLA-4 costimulatory pathways in autoimmune disease of the central nervous system. Curr Opin Immunol 11(6):677-683
5. Annunziato F, Cosmi L, et al (2007) Phenotypic and functional features of human Th17 cells. J Exp Med 204(8):1849-1861
6. Anthony DC, Miller KM, et al (1998) Matrix metalloproteinase expression in an experimentallyinduced DTH model of multiple sclerosis in the rat CNS. J Neuroimmunol 87(1-2):62-72
7. Astier A, Meiffren G, et al (2006) Alterations in CD46-mediated Tr1 regulatory T cells in patients with multiple sclerosis. J Clin Invest 116(12):3252-3257
8. Awasthi A, Carrier Y, et al (2007) A dominant function for interleukin 27 in generating interleukin 10-producing anti-inflammatory T cells. Nat Immunol 8(12):1380-1389
9. Babbe H, Roers A, et al (2000) Clonal expansions of CD8(+) T cells dominate the T cell infiltrate in active multiple sclerosis lesions as shown by micromanipulation and single cell polymerase chain reaction. J Exp Med 192(3):393-404
10. Babinski J (1885) Recherches sur l'anatomie pathologique de la sclérose en plaques et etude comparative des diverses varietes de la scléroses de la moelle. Arch Physiol 2-6:186-207
11. Baecher-Allan C, Brown JA, et al (2001) CD4+CD25high regulatory cells in human peripheral blood. J Immunol 167(3):1245-1253
12. Baecher-Allan C, Viglietta V, et al (2002) Inhibition of human CD4(+)CD25(+high) regulatory T cell function. J Immunol 169(11):6210-6217
13. Balashov KE, Smith DR, et al (1997) Increased interleukin 12 production in progressive multiple sclerosis: induction by activated CD4+ T cells via CD40 ligand. Proc Natl Acad Sci U S A 94(2):599-603
14. Barrat FJ, Cua DJ, et al (2002) In vitro generation of interleukin 10-producing regulatory CD4(+) T cells is induced by immunosuppressive drugs and inhibited by T helper type 1 (Th1)-and Th2-inducing cytokines. J Exp Med 195(5):603-616
15. Batten M, Li J, et al (2006) Interleukin 27 limits autoimmune encephalomyelitis by suppressing the development of interleukin 17-producing T cells. Nat Immunol 7(9):929-936
16. Becher B, Durell BG, et al (2002) Experimental autoimmune encephalitis and inflammation in the absence of interleukin-12. J Clin Invest 110(4):493-497
17. Beriou G, Costantino CM, et al (2009) IL-17 producing human peripheral regulatory T cells retain suppressive function. Blood 113(18):4240-4249
18. Bettelli E, Carrier Y, et al (2006) Reciprocal developmental pathways for the generation of pathogenic effector TH17 and regulatory T cells. Nature 441(7090):235-238
19. Bettelli E, Korn T, et al (2008) Induction and effector functions of T(H)17 cells. Nature 453(7198):1051-1057
20. Bo L, Peterson JW, et al (1996) Distribution of immunoglobulin superfamily members ICAM-1,-2,-3, and the beta 2 integrin LFA-1 in multiple sclerosis lesions. J Neuropathol Exp Neurol 55(10):1060-1072
21. Carboni S, Aboul-Enein F, et al (2003) CD134 plays a crucial role in the pathogenesis of EAE and is upregulated in the CNS of patients with multiple sclerosis. J Neuroimmunol 145(1-2):1-11
22. Charcot J (1868) Histologic de la sclérose en plaque. Gaz Hôp 41:554-556
23. International Multiple Sclerosis Genetics Consortium, Hafler DA, et al (2007) Risk alleles for multiple sclerosis identified by a genomewide study. N Engl J Med 357(9):851-862
24. Cua D, Sherlock J, et al (2003) Interleukin-23 rather than interleukin-12 is the critical cytokine for autoimmune inflammation of the brain. Nature 421(6924):744-748
25. Cuzner ML, Gveric D, et al (1996) The expression of tissue-type plasminogen activator, matrix metalloproteases and endogenous inhibitors in the central nervous system in multiple sclerosis: comparison of stages in lesion evolution. J Neuropathol Exp Neurol 55(12):1194-1204
26. Dardalhon V, Korn T, et al (2008) Role of Th1 and Th17 cells in organ-specific autoimmunity. J Autoimmun 31(3):252-256
27. De Jager PL, Hafler DA (2007) New therapeutic approaches for multiple sclerosis. Annu Rev Med 58:417-432
28. De Jager PL, Jia X, et al (2009a) Meta-analysis of genome scans and replication identify CD6, IRF8 and TNFRSF1A as new multiple sclerosis susceptibility loci. Nat Genet 14:14
29. De Jager PL, Baecher-Allan C, et al (2009b) The role of the CD58 locus in multiple sclerosis. Proc Natl Acad Sci USA 106(13):5264-5269
30. Dieckmann D, Bruett CH, et al (2002) Human CD4(+)CD25(+) regulatory contact-dependent T cells induce interleukin 10-producing, contact-independent type 1-like regulatory T cells [corrected]. J Exp Med 196(2):247-253
31. Dieckmann D, Plottner H, et al (2001) Ex vivo isolation and characterization of CD4(+)CD25(+) T cells with regulatory properties from human blood. J Exp Med 193(11):1303-1310
32. Duda PW, Schmied MC, et al (2000) Glatiramer acetate (Copaxone) induces degenerate, Th2-polarized immune responses in patients with multiple sclerosis. J Clin Invest 105(7):967-976
33. Elovaara I, Ukkonen M, et al (2000) Adhesion molecules in multiple sclerosis: relation to subtypes of disease and methylprednisolone therapy. Arch Neurol 57(4):546-551
34. Elyaman W, Kivisäkk P, et al (2008) Distinct functions of autoreactive memory and effector CD4+ T cells in experimental autoimmune encephalomyelitis. Am J Pathol 173(2):411-422
35. Engelhardt B, Ransohoff R (2005) The ins and outs of T-lymphocyte trafficking to the CNS: anatomical sites and moleclar mechanisms. Trends Immunol 26(9):485-495
36. Fontenot JD, Rasmussen JP, et al (2005) Regulatory T cell lineage specification by the forkhead transcription factor foxp3. Immunity 22(3):329-341
37. Genovese MC, Becker JC, et al (2005) Abatacept for rheumatoid arthritis refractory to tumor necrosis factor alpha inhibition. N Engl J Med 353(11):1114-1123
38. Giovannoni G, Cutter GR, et al (2006) Infectious causes of multiple sclerosis. Lancet Neurol 5(10):887-894
39. Graber JJ, Allie SR, et al (2008) Interleukin-17 in transverse myelitis and multiple sclerosis. J Neuroimmunol 196(1-2):124-132
40. Groux H, Bigler M, et al (1998) Inhibitory and stimulatory effects of IL-10 on human CD8+ T cells. J Immunol 160(7):3188-3193
41. Groux H, O'Garra A, et al (1997) A CD4+ T-cell subset inhibits antigen-specific T-cell responses and prevents colitis. Nature 389(6652):737-742
42. Hafler DA (2004) Multiple sclerosis. J Clin Invest 113(6):788-794
43. Hafler DA, Fox DA, et al (1985) In vivo activated T lymphocytes in the peripheral blood and cerebrospinal fluid of patients with multiple sclerosis. N Engl J Med 312(22):1405-1411
44. Hafler JP, Maier LM, et al (2009) CD226 Gly307Ser association with multiple autoimmune diseases. Genes Immun 10(1):5-10
45. Harding FA, McArthur JG, et al (1992) CD28-mediated signalling co-stimulates murine T-cells and prevents induction of anergy in T-cell clones. Nature 356(6370):607-609
46. Harrington L, Hatton R, et al (2005) Interleukin 17-producing CD4+ effector T cells develop via a lineage distinct from the T helper type 1 and 2 lineages. Nat Immunol 6(11):1123-1132
47. Hauser SL, Bhan AK, et al (1986) Immunohistochemical analysis of the cellular infiltrate in multiple sclerosis lesions. Ann Neurol 19(6):578-587
48. Huan J, Culbertson N, et al (2005) Decreased FOXP3 levels in multiple sclerosis patients. J Neurosci Res 81(1):45-52
49. Ichiyama K, Yoshida H, et al (2008) Foxp3 inhibits RORgammat-mediated IL-17A mRNA transcription through direct interaction with RORgammat. J Biol Chem 283(25):17003-17008
50. Ishizu T, Osoegawa M, et al (2005) Intrathecal activation of the IL-17/IL-8 axis in opticospinal multiple sclerosis. Brain 128(Pt 5):988-1002
51. Ivanov I, McKenzie BS, et al (2006) The orphan nuclear receptor RORgammat directs the differentiation program of proinflammatory IL-17+ T helper cells. Cell 126(6):1121-1133
52. Jenkins MK, Taylor PS, et al (1991) CD28 delivers a costimulatory signal involved in antigenspecific IL-2 production by human T cells. J Immunol 147(8):2461-2466
53. Johnson KP, Brooks BR, et al (2001) Copolymer 1 reduces relapse rate and improves disability in relapsing-remitting multiple sclerosis: results of a phase III multicenter, double-blind, placebocontrolled trial. 1995. Neurology 57(12 Suppl 5):S16-S24
54. Jonuleit H, Schmitt E, et al (2002) Infectious tolerance: human CD25(+) regulatory T cells convey suppressor activity to conventional CD4(+) T helper cells. J Exp Med 196(2):255-260
55. Kabat EA, Glusman M, et al (1948) Quantitative estimation of the albumin and gamma globulin in normal and pathologic cerebrospinal fluid by immunochemical methods. Am J Med 4(5): 653-662
56. Karandikar NJ, Vanderlugt CL, et al (1996) CTLA-4: a negative regulator of autoimmune disease. J Exp Med 184(2):783-788
57. Kebir H, Kreymborg K, et al (2007) Human TH17 lymphocytes promote blood-brain barrier disruption and central nervous system inflammation. Nat Med 13(10):1173-1175
58. Keir ME, Sharpe AH (2005) The B7/CD28 costimulatory family in autoimmunity. Immunol Rev 204:128-143
59. Kemper C, Chan AC, et al (2003) Activation of human CD4+ cells with CD3 and CD46 induces a T-regulatory cell 1 phenotype. Nature 421(6921):388-392
60. Kieseier BC, Seifert T, et al (1999) Matrix metalloproteinases in inflammatory demyelination: targets for treatment. Neurology 53(1):20-25
61. Koguchi K, Anderson D, et al (2006) Dysregulated T cell expression of TIM3 in multiple sclerosis. J Exp Med 203(6):1413-1418
62. Korn T, Bettelli E, et al (2007) IL-21 initiates an alternative pathway to induce proinflammatory T(H)17 cells. Nature 448(7152):484-487
63. Korn T, Reddy J, et al (2007) Myelin-specific regulatory T cells accumulate in the CNS but fail to control autoimmune inflammation. Nat Med 13(4):423-431
64. Kostianovsky AM, Maier LM, et al (2008) Astrocytic regulation of human monocytic/microglial activation. J Immunol 181(8):5425-5432
65. Kroenke MA, Carlson TJ, et al (2008) IL-12-and IL-23-modulated T cells induce distinct types of EAE based on histology, CNS chemokine profile, and response to cytokine inhibition. J Exp Med 205(7):1535-1541
66. Krummel MF, Allison JP (1996) CTLA-4 engagement inhibits IL-2 accumulation and cell cycle progression upon activation of resting T cells. J Exp Med 183(6):2533-2540
67. Kuhn R, Lohler J, et al (1993) Interleukin-10-deficient mice develop chronic enterocolitis. Cell 75(2):263-274
68. Kulkarni AB, Huh CG, et al (1993) Transforming growth factor beta 1 null mutation in mice causes excessive inflammatory response and early death. Proc Natl Acad Sci U S A 90(2):770-774
69. Lafferty KJ, Woolnough J (1977) The origin and mechanism of the allograft reaction. Immunol Rev 35:231-262
70. Langrish CL, Chen Y, et al (2005) IL-23 drives a pathogenic T cell population that induces autoimmune inflammation. J Exp Med 201(2):233-240
71. Lassmann H, Raine CS, et al (1998) Immunopathology of multiple sclerosis: report on an international meeting held at the Institute of Neurology of the University of Vienna. J Neuroimmunol 86(2):213-217
72. Lee YK, Turner H, et al (2009) Late developmental plasticity in the T helper 17 lineage. Immunity 30(1):92-107
73. Lehnardt S, Massillon L, et al (2003) Activation of innate immunity in the CNS triggers neurodegeneration trough a Toll-like receptor 4-dependent pathway. Proc Natl Acad Sci U S A 100(14):8514-8519
74. Leppert D, Waubant E, et al (1995) T cell gelatinases mediate basement membrane transmigration in vitro. J Immunol 154(9):4379-4389
75. Levings MK, Sangregorio R, et al (2001) IFN-alpha and IL-10 induce the differentiation of human type 1 T regulatory cells. J Immunol 166(9):5530-5539
76. Liang SC, Tan XY, et al (2006) Interleukin (IL)-22 and IL-17 are coexpressed by Th17 cells and cooperatively enhance expression of antimicrobial peptides. J Exp Med 203(10):2271-2279
77. Liu W, Putnam AL, et al (2006) CD127 expression inversely correlates with FoxP3 and suppressive function of human CD4+ T reg cells. J Exp Med 203(7):1701-1711
78. Lock C, Hermans G, et al (2002) Gene-microarray analysis of multiple sclerosis lesions yields new targets validated in autoimmune encephalomyelitis. Nat Med 8(5):500-508
79. Maeda A, Sobel RA (1996) Matrix metalloproteinases in the normal human central nervous system, microglial nodules, and multiple sclerosis lesions. J Neuropathol Exp Neurol 55(3):300-309
80. Manel N, Unutmaz D, et al (2008) The differentiation of human T(H)-17 cells requires transforming growth factor-beta and induction of the nuclear receptor RORgammat. Nat Immunol 9(6): 641-649
81. Markovic-Plese S, Cortese I, et al (2001) CD4+CD28-costimulation- independent T cells in multiple sclerosis. J Clin Invest 108(8):1185-1194
82. Mathur AN, Chang HC, et al (2006) T-bet is a critical determinant in the instability of the IL-17-secreting T-helper phenotype. Blood 108(5):1595-1601
83. Matusevicius D, Kivisäkk P, et al (1999) Interleukin-17 mRNA expression in blood and CSF mononuclear cells is augmented in multiple sclerosis. Mult Scler 5(2):101-104
84. McGeachy MJ, Cua DJ (2007) The link between IL-23 and Th17 cell-mediated immune pathologies. Semin Immunol 19(6):372-376
85. Meylan F, Davidson TS, et al (2008) The TNF-family receptor DR3 is essential for diverse T-cellmediated inflammatory diseases. Immunity 29(1):79-89
86. Miller SD, Vanderlugt CL, et al (1995) Blockade of CD28/B7-1 interaction prevents epitope spreading and clinical relapses of murine EAE. Immunity 3(6):739-745
87. Monje ML, Toda H, et al (2003) Inflammatory blockade restores adult hippocampal neurogenesis. Science 302(5651):1760-1765
88. Monney L, Sabatos CA, et al (2002) Th1-specific cell surface protein Tim-3 regulates macrophage activation and severity of an autoimmune disease. Nature 415(6871):536-541
89. Montes M, Zhang X, et al (2008) Oligoclonal myelin-reactive T-cell infiltrates derived from multiple sclerosis lesions are enriched in Th17 cells. Clin Immunol
90. Moore KW, de Waal Malefyt R, et al (2001) Interleukin-10 and the interleukin-10 receptor. Annu Rev Immunol 19:683-765
91. Mosmann TR, Coffman RL (1989) TH1 and TH2 cells: different patterns of lymphokine secretion lead to different functional properties. Annu Rev Immunol 7:145-173
92. Munger KL, Zhang SM, et al (2004) Vitamin D intake and incidence of multiple sclerosis. Neurology 62(1):60-65
93. Nakae S, Iwakura Y, et al (2007) Phenotypic differences between Th1 and Th17 cells and negative regulation of Th1 cell differentiation by IL-17. J Leukoc Biol 81(5):1258-1268
94. Navikas V, Link J, et al (1995) Increased mRNA expression of IL-10 in mononuclear cells in multiple sclerosis and optic neuritis. Scand J Immunol 41(2):171-178
95. Neuhaus O, Farina C, et al (2001) Mechanisms of action of glatiramer acetate in multiple sclerosis. Neurology 56(6):702-708
96. Nurieva R, Yang X, et al (2007) Essential autocrine regulation by IL-21 in the generation of inflammatory T cells. Nature 448(7152):480-483
97. Oliveira EM, Bar-Or A, et al (2003) CTLA-4 dysregulation in the activation of myelin basic protein reactive T cells may distinguish patients with multiple sclerosis from healthy controls. J Autoimmun 20(1):71-81
98. Ota K, Matsui M, et al (1990) T-cell recognition of an immunodominant myelin basic protein epitope in multiple sclerosis. Nature 346(6280):183-187
99. Panitch HS, Hirsch RL, et al (1987) Exacerbations of multiple sclerosis in patients treated with gamma interferon. Lancet 1(8538):893-895
100. Park H, Li Z, et al (2005) A distinct lineage of CD4 T cells regulates tissue inflammation by producing interleukin 17. Nat Immunol 6(11):1133-1141
101. Petereit HF, Pukrop R, et al (2003) Low interleukin-10 production is associated with higher disability and MRI lesion load in secondary progressive multiple sclerosis. J Neurol Sci 206(2):209-214
102. Pette M, Fujita K, et al (1990) Myelin basic protein-specific T lymphocyte lines from MS patients and healthy individuals. Neurology 40(11):1770-1776
103. Prineas J (1975) Pathology of the early lesion in multiple sclerosis. Hum Pathol 6(5):531-554
104. Prineas JW, Wright RG (1978) Macrophages, lymphocytes, and plasma cells in the perivascular compartment in chronic multiple sclerosis. Lab Invest 38(4):409-421
105. Raine CS (1994) The Dale E. McFarlin Memorial Lecture: the immunology of the multiple sclerosis lesion. Ann Neurol 36(Suppl):S61-S72
106. Read S, Malmstrom V, et al (2000) 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 192(2):295-302
107. Reijonen H, Novak EJ, et al (2002) Detection of GAD65-specific T-cells by major histocompatibility complex class II tetramers in type 1 diabetic patients and at-risk subjects. Diabetes 51(5):1375-1382
108. Rivers TM, Schwentker FF (1935) Encephalomyelitis accompanied by myelin destruction experimentally produced in monkeys. J Exp Med 61:689-702
109. Sakaguchi S, Fukuma K, et al (1985) Organ-specific autoimmune diseases induced in mice by elimination of T cell subset. I. Evidence for the active participation of T cells in natural selftolerance; deficit of a T cell subset as a possible cause of autoimmune disease. J Exp Med 161(1):72-87
110. Sakaguchi S, Yamaguchi T, et al (2008) Regulatory T cells and immune tolerance. Cell 133(5):775-787
111. Salama AD, Chitnis T, et al (2003) Critical role of the programmed death-1 (PD-1) pathway in regulation of experimental autoimmune encephalomyelitis. J Exp Med 198(1):71-78
112. Scholz C, Patton KT, et al (1998) Expansion of autoreactive T cells in multiple sclerosis is independent of exogenous B7 costimulation. J Immunol 160(3):1532-1538
113. Seddiki N, Santner-Nanan B, et al (2006) Expression of interleukin (IL)-2 and IL-7 receptors discriminates between human regulatory and activated T cells. J Exp Med 203(7):1693-1700
114. Shevach EM, McHugh RS, et al (2001) Control of T-cell activation by CD4+ CD25+ suppressor T cells. Immunol Rev 182:58-67
115. Shull MM, Ormsby I, et al (1992) Targeted disruption of the mouse transforming growth factor-beta 1 gene results in multifocal inflammatory disease. Nature 359(6397):693-699
116. Sobel RA, Mitchell ME, et al (1990) Intercellular adhesion molecule-1 (ICAM-1) in cellular immune reactions in the human central nervous system. Am J Pathol 136(6):1309-1316
117. Soldan SS, Alvarez Retuerto AI, et al (2004) Dysregulation of IL-10 and IL-12p40 in secondary progressive multiple sclerosis. J Neuroimmunol 146(1-2):209-215
118. Sørensen TL, Tani M, et al (1999) Expression of specific chemokines and chemokine receptors in the central nervous system of multiple sclerosis patients. J Clin Invest 103(6):807-815
119. Sporici RA, Beswick RL, et al (2001) ICOS ligand costimulation is required for T-cell encephalitogenicity. Clin Immunol 100(3):277-288
120. Springer TA (1994) Traffic signals for lymphocyte recirculation and leukocyte emigration: the multistep paradigm. Cell 76(2):301-314
121. Stromnes I, Cerretti L, et al (2008) Differential regulation of central nervous system autoimmunity by T(H)1 and T(H)17 cells. Nat Med 14(3):337-342
122. Stumhofer J, Laurence A, et al (2006) Interleukin 27 negatively regulates the development of interleukin 17-producing T helper cells during chronic inflammation of the central nervous system. Nat Immunol 7(9):937-945
123. Trajkovic V, Vuckovic O, et al (2004) Astrocyte-induced regulatory T cells mitigate CNS autoimmunity. Glia 47(2):168-179
124. Traugott U, Reinherz EL, et al (1983) Multiple sclerosis: distribution of T cell subsets within active chronic lesions. Science 219(4582):308-310
125. Tzartos JS, Friese MA, et al (2008) Interleukin-17 production in central nervous system-infiltrating T cells and glial cells is associated with active disease in multiple sclerosis. Am J Pathol 172(1):146-155
126. Vaknin-Dembinsky A, Balashov K, et al (2006) IL-23 is increased in dendritic cells in multiple sclerosis and down-regulation of IL-23 by antisense oligos increases dendritic cell IL-10 production. J Immunol 176(12):7768-7774
127. van Boxel-Dezaire AH, Hoff SC, et al (1999) Decreased interleukin-10 and increased interleukin-12p40 mRNA are associated with disease activity and characterize different disease stages in multiple sclerosis. Ann Neurol 45(6):695-703
128. Veldhoen M, Hocking RJ, et al (2006) TGFbeta in the context of an inflammatory cytokine milieu supports de novo differentiation of IL-17-producing T cells. Immunity 24(2):179-189
129. Venken K, Hellings N, et al (2006) 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 83(8):1432-1446
130. Vieira PL, Christensen JR, et al (2004) IL-10-secreting regulatory T cells do not express Foxp3 but have comparable regulatory function to naturally occurring CD4+CD25+ regulatory T cells. J Immunol 172(10):5986-5993
131. Viglietta V, Baecher-Allan C, et al (2004) Loss of functional suppression by CD4+CD25+ regulatory T cells in patients with multiple sclerosis. J Exp Med 199(7):971-979
132. Viglietta V, Bourcier K, et al (2008) CTLA4Ig treatment in patients with multiple sclerosis: an open-label, phase 1 clinical trial. Neurology 71(12):917-924
133. Volpe E, Servant N, et al (2008) A critical function for transforming growth factor-beta, interleukin 23 and proinflammatory cytokines in driving and modulating human T(H)-17 responses. Nat Immunol 9(6):650-657
134. Walunas TL, Lenschow DJ, et al (1994) CTLA-4 can function as a negative regulator of T-cell activation. Immunity 1(5):405-413
135. Wang J, Ioan-Facsinay A, et al (2007) Transient expression of FOXP3 in human activated nonregulatory CD4+ T cells. Eur J Immunol 37(1):129-138
136. Washington R, Burton J, et al (1994) Expression of immunologically relevant endothelial cell activation antigens on isolated central nervous system microvessels from patients with multiple sclerosis. Ann Neurol 35(1):89-97
137. Windhagen A, Newcombe J, et al (1995) Expression of costimulatory molecules B7-1 (CD80), B7-2 (CD86), and interleukin 12 cytokine in multiple sclerosis lesions. J Exp Med 182(6):1985-1996
138. Wucherpfennig KW, Newcombe J, et al (1992a) Gamma delta T-cell receptor repertoire in acute multiple sclerosis lesions. Proc Natl Acad Sci U S A 89(10):4588-4592
139. Wucherpfennig KW, Newcombe J, et al (1992b). T cell receptor V alpha-V beta repertoire and cytokine gene expression in active multiple sclerosis lesions. J Exp Med 175(4):993-1002
140. Xu L, Kitani A, et al (2007) Cutting edge: regulatory T cells induce CD4+CD25-Foxp3-T cells or are self-induced to become Th17 cells in the absence of exogenous TGF-beta. J Immunol 178(11):6725-6729
141. Yang L, Anderson D, et al (2008) IL-21 and TGF-beta are required for differentiation of human T(H)17 cells. Nature 454(7202):350-352
142. Yao Z, Painter SL, et al (1995) Human IL-17: a novel cytokine derived from T cells. J Immunol 155(12):5483-5486
143. Yeo TW, De Jager PL, et al (2007) A second major histocompatibility complex susceptibility locus for multiple sclerosis. Ann Neurol 61(3):228-236
144. Yong VW, Krekoski CA, et al (1998) Matrix metalloproteinases and diseases of the CNS. Trends Neurosci 21(2):75-80
145. Yoshida H, Imaizumi T, et al (2001) Interleukin-1beta stimulates galectin-9 expression in human astrocytes. Neuroreport 12(17):3755-3758
146. Zamvil S, Nelson P, et al (1985) T-cell clones specific for myelin basic protein induce chronic relapsing paralysis and demyelination. Nature 317(6035):355-358
147. Zhang GX, Baker CM, et al (2000) Chemokines and chemokine receptors in the pathogenesis of multiple sclerosis. Mult Scler 6(1):3-13
148. Zhang J, Markovic-Plese S, et al (1994) 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 179(3):973-984
149. Zhou L, Lopes J, et al (2008) TGF-beta-induced Foxp3 inhibits T(H)17 cell differentiation by antagonizing RORgammat function. Nature 453(7192):236-240
150. Zhu C, Anderson AC, et al (2005) The Tim-3 ligand galectin-9 negatively regulates T helper type 1 immunity. Nat Immunol 6(12):1245-1252