Skip to main content Accessibility help
×
Home
  • Get access
    Check if you have access via personal or institutional login
  • Cited by 4
  • Print publication year: 2011
  • Online publication date: December 2011

3 - The immunology of multiple sclerosis

from Section I - Introduction

References

1. Bar-Or A. The immunology of multiple sclerosis. Semin Neurol 2008; 28(1):29–45.
2. Banwell B, Bar-Or A, Cheung R, et al. Abnormal T-cell reactivities in childhood inflammatory demyelinating disease and type 1 diabetes. Ann Neurol 2008; 63(1):98–111.
3. Oksenberg JR, Baranzini SE. Multiple sclerosis genetics–is the glass half full, or half empty? Nat Rev Neurol; 6(8):429–37.
4. Okuda DT, Srinivasan R, Oksenberg JR, et al. Genotype–phenotype correlations in multiple sclerosis: HLA genes influence disease severity inferred by 1HMR spectroscopy and MRI measures. Brain, 2009; 132(1):250–9.
5. O’Brien M, Lonergan R, Costelloe L, et al. OAS1: a multiple sclerosis susceptibility gene that influences disease severity. Neurology 2010; 75(5):411–18.
6. Baranzini SE, Mudge J, van Velkinburgh JC, et al. Genome, epigenome and RNA sequences of monozygotic twins discordant for multiple sclerosis. Nature; 464(7293):1351–6.
7. Cserr HF, Harling-Berg CJ, Knopf PM. Drainage of brain extracellular fluid into blood and deep cervical lymph and its immunological significance. Brain Pathol; 2:269–76.
8. Weller RO, Galea I, Carare RO, Minagar A. Pathophysiology of the lymphatic drainage of the central nervous system: Implications for pathogenesis and therapy of multiple sclerosis. Pathophysiology 2010; 17(4):295–306.
9. de Vos AF, van Meurs M, Brok HP, et al. Transfer of central nervous system autoantigens and presentation in secondary lymphoid organs. J Immunol 2002; 169(10):5415–23.
10. Wucherpfennig KW, Allen PM, Celada F, et al. Polyspecificity of T cell and B cell receptor recognition. Semin Immunol 2007; 19(4):216–24.
11. Wucherpfennig KW, Strominger JL. Molecular mimicry in T cell-mediated autoimmunity: viral peptides activate human T cell clones specific for myelin basic protein. Cell 1995 10; 80(5):695–705.
12. Lang HL, Jacobsen H, Ikemizu S, et al. A functional and structural basis for TCR cross-reactivity in multiple sclerosis. Nat Immunol 2002; 3(10):940–3.
13. Vanderlugt CL, Miller SD. Epitope spreading in immune-mediated diseases: implications for immunotherapy. Nat Rev Immunol 2002; 2(2):85–95.
14. Giacomini PS, Bar-Or A. Antigen-specific therapies in multiple sclerosis. Expert Opin Emerg Drugs 2009; 14(3):551–60.
15. Bar-Or A, Vollmer T, Antel J, et al. Induction of antigen-specific tolerance in multiple sclerosis after immunization with DNA encoding myelin basic protein in a randomized, placebo-controlled phase 1/2 trial. Arch Neurol 2007; 64(10):1407–15.
16. Viglietta V, Bourcier K, Buckle GJ, et al. CTLA4Ig treatment in patients with multiple sclerosis: an open-label, phase 1 clinical trial. Neurology 2008; 71(12):917–24.
17. Korn T, Oukka M, Kuchroo V, Bettelli E. Th17 cells: effector T cells with inflammatory properties. Semin Immunol 2007; 19(6):362–71.
18. Bettelli E, Oukka M, Kuchroo VK. T(H)-17 cells in the circle of immunity and autoimmunity. Nat Immunol 2007; 8(4):345–50.
19. Zhu J, Paul WE. Peripheral CD4+ T-cell differentiation regulated by networks of cytokines and transcription factors. Immunol Rev; 238(1):247–62.
20. Yang Y, Weiner J, Liu Y, et al. T-bet is essential for encephalitogenicity of both Th1 and Th17 cells. J Exp Med 2009; 206(7):1549–64.
21. Du C, Liu C, Kang J, et al. MicroRNA miR-326 regulates TH-17 differentiation and is associated with the pathogenesis of multiple sclerosis. Nat Immunol 2009; 10(12):1252–9.
22. Jager A, Dardalhon V, Sobel RA, Bettelli E, Kuchroo VK. Th1, Th17, and Th9 effector cells induce experimental autoimmune encephalomyelitis with different pathological phenotypes. J Immunol 2009; 183(11):7169–77.
23. Kroenke MA, Carlson TJ, Andjelkovic AV, Segal BM. 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 2008; 205(7):1535–41.
24. Kebir H, Kreymborg K, Ifergan I, et al. Human TH17 lymphocytes promote blood–brain barrier disruption and central nervous system inflammation. Nat Med. 2007; 13(10):1173–5.
25. Ifergan I, Kebir H, Bernard M, et al. The blood-brain barrier induces differentiation of migrating monocytes into Th17-polarizing dendritic cells. Brain 2008; 131(Pt 3):785–99.
26. Kebir H, Ifergan I, Alvarez JI, et al. Preferential recruitment of interferon-gamma-expressing TH17 cells in multiple sclerosis. Ann Neurol 2009; 66(3):390–402.
27. Prinz M, Kalinke U. New lessons about old molecules: how type I interferons shape Th1/Th17-mediated autoimmunity in the CNS. Trends Mol Med; 16(8):379–86.
28. Aharoni R, Eilam R, Stock A, et al. Glatiramer acetate reduces Th-17 inflammation and induces regulatory T-cells in the CNS of mice with relapsing–remitting or chronic EAE. J Neuroimmunol 2010; 225(1–2):100–11.
29. Begum-Haque S, Sharma A, Kasper IR, et al. Downregulation of IL-17 and IL-6 in the central nervous system by glatiramer acetate in experimental autoimmune encephalomyelitis. J Neuroimmunol 2008; 204(1–2):58–65.
30. Mehling M, Lindberg R, Raulf F, et al. Th17 central memory T cells are reduced by FTY720 in patients with multiple sclerosis. Neurology; 75(5):403–10.
31. Bar-Or A, Fawaz L, Fan B, et al. Abnormal B-cell cytokine responses a trigger of T-cell-mediated disease in MS? Ann Neurol 2010; 67(4):452–61.
32. Axtell RC, de Jong BA, Boniface K, et al. T helper type 1 and 17 cells determine efficacy of interferon-beta in multiple sclerosis and experimental encephalomyelitis. Nat Med 2010; 16(4):406–12.
33. Rafei M, Campeau PM, Aguilar-Mahecha A, et al. Mesenchymal stromal cells ameliorate experimental autoimmune encephalomyelitis by inhibiting CD4 Th17 T cells in a CC chemokine ligand 2-dependent manner. J Immunol 2009; 182(10):5994–6002.
34. Darlington PJ, Boivin MN, Renoux C, et al. Reciprocal Th1 and Th17 regulation by mesenchymal stem cells: Implication for multiple sclerosis. Ann Neurol 2010; 68(4):540–5.
35. Reboldi A, Coisne C, Baumjohann D, et al. C-C chemokine receptor 6-regulated entry of TH-17 cells into the CNS through the choroid plexus is required for the initiation of EAE. Nat Immunol 2009; 10(5):514–23.
36. Ponomarev ED, Shriver LP, Maresz K, Pedras-Vasconcelos J, Verthelyi D, Dittel BN. GM-CSF production by autoreactive T cells is required for the activation of microglial cells and the onset of experimental autoimmune encephalomyelitis. J Immunol 2007; 178(1):39–48.
37. Nowak EC, Weaver CT, Turner H, et al. IL-9 as a mediator of Th17-driven inflammatory disease. J Exp Med 2009; 206(8):1653–60.
38. Elyaman W, Bradshaw EM, Uyttenhove C, et al. IL-9 induces differentiation of TH17 cells and enhances function of FoxP3+ natural regulatory T cells. Proc Natl Acad Sci USA 2009; 106(31):12885–90.
39. Beriou G, Bradshaw EM, Lozano E, et al. TGF-beta induces IL-9 production from human Th17 cells. J Immunol 2010; 185(1):46–54.
40. Genain CP, Abel K, Belmar N, et al. Late complications of immune deviation therapy in a nonhuman primate. Science 1996; 274(5295):2054–7.
41. Pedotti R, Mitchell D, Wedemeyer J, et al. An unexpected version of horror autotoxicus: anaphylactic shock to a self-peptide. Nat Immunol 2001; 2(3):216–22.
42. Cvetanovich GL, Hafler DA. Human regulatory T cells in autoimmune diseases. Curr Opin Immunol 2010; 22(6):753–60.
43. Huang YH, Zozulya AL, Weidenfeller C, Schwab N, Wiendl H. T cell suppression by naturally occurring HLA-G-expressing regulatory CD4+ T cells is IL-10-dependent and reversible. J Leukoc Biol 2009; 86(2):273–81.
44. Gandhi R, Farez MF, Wang Y, Kozoriz D, Quintana FJ, Weiner HL. Cutting edge: human latency-associated peptide+ T cells: a novel regulatory T cell subset. J Immunol 2010; 184(9):4620–4.
45. Schneider-Hohendorf T, Stenner MP, Weidenfeller C, et al. Regulatory T cells exhibit enhanced migratory characteristics, a feature impaired in patients with multiple sclerosis. Eur J Immunol 2010; 40(12):3581–90.
46. Fletcher JM, Lonergan R, Costelloe L, et al. CD39+Foxp3 +regulatory T Cells suppress pathogenic Th17 cells and are impaired in multiple sclerosis. J Immunol 2009; 183(11):7602–10.
47. Astier AL, Meiffren G, Freeman S, Hafler DA. Alterations in CD46-mediated Tr1 regulatory T cells in patients with multiple sclerosis. J Clin Invest 2006; 116(12):3252–7.
48. Korn T, Reddy J, Gao W, et al. Myelin-specific regulatory T cells accumulate in the CNS but fail to control autoimmune inflammation. Nat Med 2007; 13(4):423–31.
49. Genc K, Dona DL, Reder AT. Increased CD80(+) B cells in active multiple sclerosis and reversal by interferon beta-1b therapy. J Clin Invest 1997; 99(11):2664–71.
50. Bar-Or A, Oliveira EM, Anderson DE, et al. Immunological memory: contribution of memory B cells expressing costimulatory molecules in the resting state. J Immunol 2001; 167(10):5669–77.
51. Duddy ME, Alter A, Bar-Or A. Distinct profiles of human B cell effector cytokines: a role in immune regulation? J Immunol 2004; 172(6):3422–7.
52. Duddy M, Niino M, Adatia F, et al. Distinct effector cytokine profiles of memory and naive human B cell subsets and implication in multiple sclerosis. J Immunol 2007; 178(10):6092–9.
53. Correale J, Farez M, Razzitte G. Helminth infections associated with multiple sclerosis induce regulatory B cells. Ann Neurol 2008; 64(2):187–99.
54. Harp CT, Ireland S, Davis LS, et al. Memory B cells from a subset of treatment-naive relapsing–remitting multiple sclerosis patients elicit CD4(+) T-cell proliferation and IFN-gamma production in response to myelin basic protein and myelin oligodendrocyte glycoprotein. Eur J Immunol 2010; 40(10):2942–56.
55. Matsushita T, Yanaba K, Bouaziz JD, Fujimoto M, Tedder TF. Regulatory B cells inhibit EAE initiation in mice while other B cells promote disease progression. J Clin Invest 2008; 118(10):3420–30.
56. Weber MS, Prod'homme T, Patarroyo JC, et al. B-cell activation influences T-cell polarization and outcome of anti-CD20 B-cell depletion in central nervous system autoimmunity. Ann Neurol 2010; 68(3):369–83.
57. Martin JF, Perry JS, Jakhete NR, Wang X, Bielekova B. An IL-2 paradox: blocking CD25 on T cells induces IL-2-driven activation of CD56(bright) NK cells. J Immunol 2010; 185(2):1311–20.
58. Kim HJ, Ifergan I, Antel JP, et al. Type 2 monocyte and microglia differentiation mediated by glatiramer acetate therapy in patients with multiple sclerosis. J Immunol 2004; 172(11):7144–53.
59. Weber MS, Starck M, Wagenpfeil S, Meinl E, Hohlfeld R, Farina C. Multiple sclerosis: glatiramer acetate inhibits monocyte reactivity in vitro and in vivo. Brain 2004; 127(Pt 6):1370–8.
60. Schwab N, Zozulya AL, Kieseier BC, Toyka KV, Wiendl H. An imbalance of two functionally and phenotypically different subsets of plasmacytoid dendritic cells characterizes the dysfunctional immune regulation in multiple sclerosis. J Immunol 2010; 184(9):5368–74.
61. Racke MK, Drew PD. Toll-like receptors in multiple sclerosis. Curr Top Microbiol Immunol 2009; 336:155–68.
62. Ransohoff RM. Mechanisms of inflammation in MS tissue: adhesion molecules and chemokines. J Neuroimmunol 1999; 98(1):57–68.
63. Cayrol R, Wosik K, Berard JL, et al. Activated leukocyte cell adhesion molecule promotes leukocyte trafficking into the central nervous system. Nat Immunol 2008; 9(2):137–45.
64. Ifergan I, Kebir H, Terouz S, et al. Role of Ninjurin-1 in the migration of myeloid cells to CNS inflammatory lesions. Ann Neurol. 2011; in press.
65. Bartholomaus I, Kawakami N, Odoardi F, et al. Effector T cell interactions with meningeal vascular structures in nascent autoimmune CNS lesions. Nature 2009; 462(7269):94–8.
66. Ransohoff RM, Kivisakk P, Kidd G. Three or more routes for leukocyte migration into the central nervous system. Nat Rev Immunol 2003; 3(7):569–81.
67. Holman DW, Klein RS, Ransohoff RM. The blood–brain barrier, chemokines and multiple sclerosis. Biochim Biophys Acta 2011; 1812(2):220–30.
68. Hohlfeld R, Meinl E, Dornmair K. B- and T-cell responses in multiple sclerosis: novel approaches offer new insights. J Neurol Sci 2008; 274(1–2):5–8.
69. Ransohoff RM, Cardona AE. The myeloid cells of the central nervous system parenchyma. Nature 2010; 468(7321):253–62.
70. Li Y, Chu N, Hu A, Gran B, Rostami A, Zhang GX. Increased IL-23p19 expression in multiple sclerosis lesions and its induction in microglia. Brain 2007; 130(Pt 2):490–501.
71. Durafourt BA, Lambert C, Johnson TA, Blain M, Bar-Or A, Antel JP. Differential responses of human microglia and blood-derived myeloid cells to FTY720. J Neuroimmunol 2011; 230 (1–2):10–16.
72. Lambert C, Desbarats J, Arbour N, et al. Dendritic cell differentiation signals induce anti-inflammatory properties in human adult microglia. J Immunol 2008; 181(12):8288–97.
73. Constantinescu CS, Tani M, Ransohoff RM, et al. Astrocytes as antigen-presenting cells: expression of IL-12/IL-23. J Neurochem 2005; 95(2):331–40.
74. Giuliani F, Goodyer CG, Antel JP, Yong VW. Vulnerability of human neurons to T cell-mediated cytotoxicity. J Immunol 2003; 171(1):368–79.
75. Neumann H, Medana IM, Bauer J, Lassmann H. Cytotoxic T lymphocytes in autoimmune and degenerative CNS diseases. Trends Neurosci 2002; 25(6):313–19.
76. Melzer N, Meuth SG, Wiendl H. CD8+ T cells and neuronal damage: direct and collateral mechanisms of cytotoxicity and impaired electrical excitability. FASEB J 2009; 23(11):3659–73.
77. Wang T, Lee MH, Johnson T, et al. Activated T-cells inhibit neurogenesis by releasing granzyme B: rescue by Kv1.3 blockers. J Neurosci 2010; 30(14):5020–7.
78. Darlington PJ, Podjaski C, Horn KE, et al. Innate immune-mediated neuronal injury consequent to loss of astrocytes. J Neuropathol Exp Neurol 2008; 67(6):590–9.
79. Babbe H, Roers A, Waisman A, et al. 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 2000; 192(3):393–404.
80. Hoftberger R, Aboul-Enein F, Brueck W, et al. Expression of major histocompatibility complex class I molecules on the different cell types in multiple sclerosis lesions. Brain Pathol 2004; 14(1):43–50.
81. Skulina C, Schmidt S, Dornmair K, et al. Multiple sclerosis: brain-infiltrating CD8+ T cells persist as clonal expansions in the cerebrospinal fluid and blood. Proc Natl Acad Sci USA 2004; 101(8):2428–33.
82. Tsuchida T, Parker KC, Turner RV, McFarland HF, Coligan JE, Biddison WE. Autoreactive CD8+ T-cell responses to human myelin protein-derived peptides. Proc Natl Acad Sci USA 1994; 91(23):10859–63.
83. Buckle GJ, Hollsberg P, Hafler DA. Activated CD8+ T cells in secondary progressive MS secrete lymphotoxin. Neurology 2003; 60(4):702–5.
84. Crawford MP, Yan SX, Ortega SB, et al. High prevalence of autoreactive, neuroantigen-specific CD8+ T cells in multiple sclerosis revealed by novel flow cytometric assay. Blood 2004; 103(11):4222–31.
85. Goverman J. Autoimmune T cell responses in the central nervous system. Nat Rev Immunol 2009; 9(6):393–407.
86. York NR, Mendoza JP, Ortega SB, et al. Immune regulatory CNS-reactive CD8+T cells in experimental autoimmune encephalomyelitis. J Autoimmun. 2010; 35(1):33–44.
87. Harp C, Lee J, Lambracht-Washington D, et al. Cerebrospinal fluid B cells from multiple sclerosis patients are subject to normal germinal center selection. J Neuroimmunol 2007; 183(1–2):189–99.
88. Obermeier B, Mentele R, Malotka J, et al. Matching of oligoclonal immunoglobulin transcriptomes and proteomes of cerebrospinal fluid in multiple sclerosis. Nat Med 2008; 14(6):688–93.
89. von Budingen HC, Gulati M, Kuenzle S, Fischer K, Rupprecht TA, Goebels N. Clonally expanded plasma cells in the cerebrospinal fluid of patients with central nervous system autoimmune demyelination produce “oligoclonal bands.” J Neuroimmunol 2010; 218(1–2):134–9.
90. Archelos JJ, Storch MK, Hartung HP. The role of B cells and autoantibodies in multiple sclerosis. Ann Neurol 2000; 47(6):694–706.
91. Cross AH, Trotter JL, Lyons J. B cells and antibodies in CNS demyelinating disease. J Neuroimmunol 2001; 112(1–2):1–14.
92. Fraussen J, Vrolix K, Martinez Martinez P, et al. B cell characterization and reactivity analysis in multiple sclerosis. Autoimmun Rev 2009; 8(8):654–8.
93. Storch MK, Piddlesden S, Haltia M, Iivanainen M, Morgan P, Lassmann H. Multiple sclerosis: in situ evidence for antibody- and complement-mediated demyelination. Ann Neurol 1998; 43(4):465–71.
94. Genain CP, Cannella B, Hauser SL, Raine CS. Identification of autoantibodies associated with myelin damage in multiple sclerosis. Nat Med 1999; 5(2):170–5.
95. O’Connor KC, Appel H, Bregoli L, et al. Antibodies from inflamed central nervous system tissue recognize myelin oligodendrocyte glycoprotein. J Immunol 2005; 175(3):1974–82.
96. Izquierdo G, Angulo S, Garcia-Moreno JM, et al. Intrathecal IgG synthesis: marker of progression in multiple sclerosis patients. Acta Neurol Scand 2002; 105(3):158–63.
97. Villar LM, Masjuan J, Gonzalez-Porque P, et al. Intrathecal IgM synthesis predicts the onset of new relapses and a worse disease course in MS. Neurology 2002; 59(4):555–9.
98. Villar LM, Sadaba MC, Roldan E, et al. Intrathecal synthesis of oligoclonal IgM against myelin lipids predicts an aggressive disease course in MS. J Clin Invest. 2005; 115(1):187–94.
99. Zeman AZ, Kidd D, McLean BN, et al. A study of oligoclonal band negative multiple sclerosis. J Neurol Neurosurg Psychiatry. 1996; 60(1):27–30.
100. O’Connor KC, Lopez-Amaya C, Gagne D, et al. Anti-myelin antibodies modulate clinical expression of childhood multiple sclerosis. J Neuroimmunol 2010; 223(1–2):92–9.
101. Genain CP, Nguyen MH, Letvin NL, et al. Antibody facilitation of multiple sclerosis-like lesions in a nonhuman primate. J Clin Invest 1995; 96(6):2966–74.
102. Klawiter EC, Piccio L, Lyons JA, Mikesell R, O’Connor KC, Cross AH. Elevated intrathecal myelin oligodendrocyte glycoprotein antibodies in multiple sclerosis. Arch Neurol 2010; 67(9):1102–8.
103. Zhou D, Srivastava R, Nessler S, et al. Identification of a pathogenic antibody response to native myelin oligodendrocyte glycoprotein in multiple sclerosis. Proc Natl Acad Sci USA 2006; 103(50):19057–62.
104. Lalive PH, Menge T, Delarasse C, et al. Antibodies to native myelin oligodendrocyte glycoprotein are serologic markers of early inflammation in multiple sclerosis. Proc Natl Acad Sci USA 2006; 103(7):2280–5.
105. O’Connor KC, McLaughlin KA, De Jager PL, et al. Self-antigen tetramers discriminate between myelin autoantibodies to native or denatured protein. Nat Med 2007; 13(2):211–17.
106. Chan A, Decard BF, Franke C, et al. Serum antibodies to conformational and linear epitopes of myelin oligodendrocyte glycoprotein are not elevated in the preclinical phase of multiple sclerosis. Mult Scler 2010; 16(10):1189–92.
107. Selter RC, Brilot F, Grummel V, et al. Antibody responses to EBV and native MOG in pediatric inflammatory demyelinating CNS diseases. Neurology 2010; 74(21):1711–15.
108. Derfuss T, Linington C, Hohlfeld R, Meinl E. Axo-glial antigens as targets in multiple sclerosis: implications for axonal and grey matter injury. J Mol Med 2010; 88(8):753–61.
109. Kanter JL, Narayana S, Ho PP, et al. Lipid microarrays identify key mediators of autoimmune brain inflammation. Nat Med 2006; 12(1):138–43.
110. Garcia-Barragan N, Villar LM, Espino M, Sadaba MC, Gonzalez-Porque P, Alvarez-Cermeno JC. Multiple sclerosis patients with anti-lipid oligoclonal IgM show early favourable response to immunomodulatory treatment. Eur J Neurol 2009; 16(3):380–5.
111. Podbielska M, Dasgupta S, Levery SB, et al. Novel myelin penta- and hexa-acetyl-galactosyl-ceramides: structural characterization and immunoreactivity in cerebrospinal fluid. J Lipid Res 2010; 51(6):1394–406.
112. Ravetch JV, Bolland S. IgG Fc receptors. Annu Rev Immunol 2001; 19:275–90.
113. Warrington AE, Asakura K, Bieber AJ, et al. Human monoclonal antibodies reactive to oligodendrocytes promote remyelination in a model of multiple sclerosis. Proc Natl Acad Sci USA 2000; 97(12):6820–5.
114. Mi S, Miller RH, Tang W, et al. Promotion of central nervous system remyelination by induced differentiation of oligodendrocyte precursor cells. Ann Neurol 2009; 65(3):304–15.
115. Reindl M, Khantane S, Ehling R, et al. Serum and cerebrospinal fluid antibodies to Nogo-A in patients with multiple sclerosis and acute neurological disorders. J Neuroimmunol 2003; 145(1–2):139–47.
116. Karnezis T, Mandemakers W, McQualter JL, et al. The neurite outgrowth inhibitor Nogo A is involved in autoimmune-mediated demyelination. Nat Neurosci 2004; 7(7):736–44.
117. Li W, Walus L, Rabacchi SA, et al. A neutralizing anti-Nogo66 receptor monoclonal antibody reverses inhibition of neurite outgrowth by central nervous system myelin. J Biol Chem 2004; 279(42):43780–8.
118. Yang Y, Liu Y, Wei P, et al. Silencing Nogo-A promotes functional recovery in demyelinating disease. Ann Neurol 2010; 67(4):498–507.
119. Magnus T, Schreiner B, Korn T, et al. Microglial expression of the B7 family member B7 homolog 1 confers strong immune inhibition: implications for immune responses and autoimmunity in the CNS. J Neurosci 2005; 25(10):2537–46.
120. Wiendl H, Feger U, Mittelbronn M, et al. Expression of the immunetolerogenic major histocompatibility molecule HLA-G in multiple sclerosis: implications for CNS immunity. Brain 2005; 128(Pt 11):2689–704.
121. Liu Y, Bando Y, Vargas-Lowy D, et al. CD200R1 agonist attenuates mechanisms of chronic disease in a murine model of multiple sclerosis. J Neurosci 2010; 30(6):2025–38.
122. Krumbholz M, Theil D, Derfuss T, et al. BAFF is produced by astrocytes and up-regulated in multiple sclerosis lesions and primary central nervous system lymphoma. J Exp Med 2005; 201(2):195–200.
123. Corcione A, Casazza S, Ferretti E, et al. Recapitulation of B cell differentiation in the central nervous system of patients with multiple sclerosis. Proc Natl Acad Sci USA 2004; 101(30):11064–9.
124. Prineas JW. Multiple sclerosis: presence of lymphatic capillaries and lymphoid tissue in the brain and spinal cord. Science. 1979; 203(4385):1123–5.
125. Serafini B, Rosicarelli B, Magliozzi R, Stigliano E, Aloisi F. Detection of ectopic B-cell follicles with germinal centers in the meninges of patients with secondary progressive multiple sclerosis. Brain Pathol 2004; 14(2):164–74.
126. Magliozzi R, Howell O, Vora A, et al. Meningeal B-cell follicles in secondary progressive multiple sclerosis associate with early onset of disease and severe cortical pathology. Brain 2007; 130(Pt 4):1089–104.
127. Vinuesa CG, Sanz I, Cook MC. Dysregulation of germinal centres in autoimmune disease. Nat Rev Immunol 2009; 9(12):845–57.
128. Piccio L, Naismith RT, Trinkaus K, et al. Changes in B- and T-lymphocyte and chemokine levels with rituximab treatment in multiple sclerosis. Arch Neurol 2010; 67(6):707–14.
129. Cross AH, Stark JL, Lauber J, Ramsbottom MJ, Lyons JA. Rituximab reduces B cells and T cells in cerebrospinal fluid of multiple sclerosis patients. J Neuroimmunol 2006; 180(1–2):63–70.
130. Freedman MS, Ruijs TC, Selin LK, Antel JP. Peripheral blood gamma-delta T cells lyse fresh human brain-derived oligodendrocytes. Ann Neurol 1991; 30(6):794–800.
131. Petermann F, Rothhammer V, Claussen MC, et al. gammadelta T cells enhance autoimmunity by restraining regulatory T-cell responses via an interleukin-23-dependent mechanism. Immunity 2010; 33(3):351–63.
132. Antel J, Owens T. Multiple sclerosis and immune regulatory cells. Brain 2004; 127(Pt 9):1915–16.
133. DeBoy CA, Rus H, Tegla C, et al. FLT-3 expression and function on microglia in multiple sclerosis. Exp Mol Pathol 2010; 89(2):109–16.
134. Martino G, Adorini L, Rieckmann P, etal. Inflammation in multiple sclerosis: the good, the bad, and the complex. Lancet Neurol 2002; 1(8):499–509.
135. Yong VW, Rivest S. Taking advantage of the systemic immune system to cure brain diseases. Neuron 2009; 64(1):55–60.
136. Villoslada P, Moreno B, Melero I, et al. Immunotherapy for neurological diseases. Clin Immunol 2008; 128(3):294–305.
137. Rodriguez M, Warrington AE, Pease LR. Invited article: human natural autoantibodies in the treatment of neurologic disease. Neurology 2009; 72(14):1269–76.
138. Skihar V, Silva C, Chojnacki A, et al. Promoting oligodendrogenesis and myelin repair using the multiple sclerosis medication glatiramer acetate. Proc Natl Acad Sci USA. 2009; 106(42):17992–7.
139. Arnon R, Aharoni R. Neuroprotection and neurogeneration in MS and its animal model EAE effected by glatiramer acetate. J Neural Transm 2009; 116(11):1443–9.
140. Miron VE, Ludwin SK, Darlington PJ, et al. Fingolimod (FTY720) enhances remyelination following demyelination of organotypic cerebellar slices. Am J Pathol 2010; 176(6):2682–94.
141. Gold R. Oral therapies for multiple sclerosis: a review of agents in phase III development or recently approved. CNS Drugs 2011; 25(1):37–52.