Immunologic aspects of multiple sclerosis

Mount Sinai Journal of Medicine

Volumn 78, Issue 2, 2011, Pages 207-220

  Boppana, Sridhar ^a   Huang, Hui ^a   Ito, Kouichi ^a   Dhib Jalbut, Suhayl ^a  

^a RUTGERS ROBERT WOOD JOHNSON MEDICAL SCHOOL   (United States)

Author keywords

cytokines; multiple sclerosis; multiple sclerosis therapies; neuroinflammation

Indexed keywords

ALEMTUZUMAB; BETA INTERFERON; CD39 ANTIGEN; CLADRIBINE; DACLIZUMAB; FINGOLIMOD; GLATIRAMER; HLA DR2 ANTIGEN; HLA E ANTIGEN; INTERLEUKIN 10; INTERLEUKIN 17; INTERLEUKIN 17F; INTERLEUKIN 1BETA; INTERLEUKIN 2 RECEPTOR ALPHA; INTERLEUKIN 21; INTERLEUKIN 22; INTERLEUKIN 23; INTERLEUKIN 7 RECEPTOR ALPHA; INTERLEUKIN 9; LAQUINIMOD; MITOXANTRONE; NATALIZUMAB; RITUXIMAB; TERIFLUNOMIDE; TRANSCRIPTION FACTOR FOXP3;

ANTIGEN PRESENTING CELL; ARTICLE; B LYMPHOCYTE; CELL FUNCTION; CYTOKINE RELEASE; DENDRITIC CELL; DISEASE COURSE; HELPER CELL; HUMAN; IMMUNOCOMPETENT CELL; IMMUNOPATHOGENESIS; LYMPHOCYTE DIFFERENTIATION; LYMPHOCYTE SUBPOPULATION; MULTIPLE SCLEROSIS; NATURAL KILLER T CELL; PHENOTYPE; REGULATORY T LYMPHOCYTE; REMISSION; TH1 CELL; TH17 CELL; TH9 CELL;

AXONS; DISEASE PROGRESSION; ENVIRONMENT; GENETIC PREDISPOSITION TO DISEASE; HUMANS; IMMUNITY; IMMUNOLOGIC FACTORS; INFLAMMATION; MULTIPLE SCLEROSIS; MYELIN SHEATH; NERVE DEGENERATION; THERAPIES, INVESTIGATIONAL;

EID: 79952998957     PISSN: 00272507     EISSN: 19317581     Source Type: Journal    
DOI: 10.1002/msj.20249     Document Type: Article

References (97)

1. Oksenberg JR, Baranzini SE., Multiple sclerosis genetics-is the glass half full, or half empty? Nat Rev Neurol 2010; 6: 429-437.
2. Ramagopalan SV, Knight JC, Ebers GC., Multiple sclerosis and the major histocompatibility complex. Curr Opin Neurol 2009; 22: 219-225.
3. Hafler DA, Compston A, Sawcer S, et al,. Risk alleles for multiple sclerosis identified by a genomewide study. N Engl J Med 2007; 357: 851-862. (Pubitemid 47347319)
4. Goverman J., Autoimmune T cell responses in the central nervous system. Nat Rev Immunol 2009; 9: 393-407.
5. Krishnamoorthy G, Wekerle H., EAE: an immunologist's magic eye. Eur J Immunol 2009; 39: 2031-2035.
6. Chastain EM, Duncan DS, Rodgers JM, et al,. The role of antigen presenting cells in multiple sclerosis. Biochim Biophys Acta 2011; 1812: 265-274.
7. Sriram S, Steiner I., Experimental allergic encephalomyelitis: a misleading model of multiple sclerosis. Ann Neurol 2005; 58: 939-945. (Pubitemid 41746884)
8. Steinman L, Zamvil SS., How to successfully apply animal studies in experimental allergic encephalomyelitis to research on multiple sclerosis. Ann Neurol 2006; 60: 12-21.
9. Granieri E, Malagu S, Casetta I, et al,. Multiple sclerosis in Italy: a reappraisal of incidence and prevalence in Ferrara. Arch Neurol 1996; 53: 793-798.
10. Pugliatti M, Sotgiu S, Solinas G, et al,. Multiple sclerosis epidemiology in Sardinia: evidence for a true increasing risk. Acta Neurol Scand 2001; 103: 20-26.
11. Granieri E, Economou NT, De Gennaro R, et al,. Multiple sclerosis in the province of Ferrara: evidence for an increasing trend. J Neurol 2007; 254: 1642-1648.
12. Franciotta D, Salvetti M, Lolli F, et al,. B cells and multiple sclerosis. Lancet Neurol 2008; 7: 852-858.
13. Correale J, Farez M., Helminth antigens modulate immune responses in cells from multiple sclerosis patients through TLR2-dependent mechanisms. J Immunol 2009; 183: 5999-6012.
14. Correale J, Ysrraelit MC, Gaitan MI., Immunomodulatory effects of vitamin D in multiple sclerosis. Brain 2009; 132: 1146-1160.
15. Sakaguchi S, Powrie F., Emerging challenges in regulatory T cell function and biology. Science 2007; 317: 627-629. (Pubitemid 47229955)
16. Lopez-Diego RS, Weiner HL., Novel therapeutic strategies for multiple sclerosis-a multifaceted adversary. Nat Rev Drug Discov 2008; 7: 909-925.
17. Viglietta V, Baecher-Allan C, Weiner HL, et al,. Loss of functional suppression by CD4+CD25+ regulatory T cells in patients with multiple sclerosis. J Exp Med 2004; 199: 971-979. (Pubitemid 38481088)
18. Leussink VI, Zettl UK, Jander S, et al,. Blockade of signaling via the very late antigen (VLA-4) and its counterligand vascular cell adhesion molecule-1 (VCAM-1) causes increased T cell apoptosis in experimental autoimmune neuritis. Acta Neuropathol 2002; 103: 131-136. (Pubitemid 36067490)
19. Jager A, Dardalhon V, Sobel RA, et al,. Th1, Th17, and Th9 effector cells induce experimental autoimmune encephalomyelitis with different pathological phenotypes. J Immunol 2009; 183: 7169-7177.
20. 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 U S A 2004; 101: 2428-2433. (Pubitemid 38269328)
21. Medana I, Martinic MA, Wekerle H, et al,. Transection of major histocompatibility complex class I-induced neurites by cytotoxic T lymphocytes. Am J Pathol 2001; 159: 809-815. (Pubitemid 32847171)
22. Giuliani F, Goodyer CG, Antel JP, et al,. Vulnerability of human neurons to T cell-mediated cytotoxicity. J Immunol 2003; 171: 368-379. (Pubitemid 36745310)
23. Chitnis T., The role of CD4 T cells in the pathogenesis of multiple sclerosis. Int Rev Neurobiol 2007; 79: 43-72.
24. Hedegaard CJ, Krakauer M, Bendtzen K, et al,. T helper cell type 1 (Th1), Th2 and Th17 responses to myelin basic protein and disease activity in multiple sclerosis. Immunology 2008; 125: 161-169.
25. Hemmer B, Cepok S, Zhou D, et al,. Multiple sclerosis-a coordinated immune attack across the blood brain barrier. Curr Neurovasc Res 2004; 1: 141-150.
26. Delgado S, Sheremata WA., The role of CD4+ T-cells in the development of MS. Neurol Res 2006; 28: 245-249. (Pubitemid 43765107)
27. Gocke AR, Cravens PD, Ben LH, et al,. T-bet regulates the fate of Th1 and Th17 lymphocytes in autoimmunity. J Immunol 2007; 178: 1341-1348. (Pubitemid 46154603)
28. Gold R, Lühder F., Interleukin-17-extended features of a key player in multiple sclerosis. Am J Pathol 2008; 172: 8-10. (Pubitemid 351186362)
29. Tesmer LA, Lundy SK, Sarkar S, et al,. Th17 cells in human disease. Immunol Rev 2008; 223: 87-113. (Pubitemid 351986173)
30. Durelli L, Conti L, Clerico M, et al,. T-helper 17 cells expand in multiple sclerosis and are inhibited by interferon-beta. Ann Neurol 2009; 65: 499-509.
31. Tzartos JS, Friese MA, Craner MJ, et al,. Interleukin-17 production in central nervous system-infiltrating T cells and glial cells is associated with active disease in multiple sclerosis. Am J Pathol 2008; 172: 146-155. (Pubitemid 351186376)
32. 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: 1173-1175. (Pubitemid 47530640)
33. Ransohoff RM., Immunology: In the beginning. Nature 2009; 462: 41-42.
34. Kebir H, Ifergan I, Alvarez JI, et al,. Preferential recruitment of interferon-gamma-expressing TH17 cells in multiple sclerosis. Ann Neurol 2009; 66: 390-402.
35. Edwards LJ, Robins RA, Constantinescu CS., Th17/Th1 phenotype in demyelinating disease. Cytokine 2010; 50: 19-23.
36. Klotz L, Burgdorf S, Dani I, et al,. The nuclear receptor PPAR gamma selectively inhibits Th17 differentiation in a T cell-intrinsic fashion and suppresses CNS autoimmunity. J Exp Med 2009; 206: 2079-2089.
37. Guo B, Chang EY, Cheng G., The type I IFN induction pathway constrains Th17-mediated autoimmune inflammation in mice. J Clin Invest 2008; 118: 1680-1690. (Pubitemid 351632372)
38. 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: 406-412.
39. Segal BM, Constantinescu CS, Raychaudhuri A, et al,. Repeated subcutaneous injections of IL12/23 p40 neutralising antibody, ustekinumab, in patients with relapsing-remitting multiple sclerosis: a phase II, double-blind, placebo-controlled, randomised, dose-ranging study. Lancet Neurol 2008; 7: 796-804.
40. Uyttenhove C, Simpson RJ, Van Snick J., Functional and structural characterization of P40, a mouse glycoprotein with T-cell growth factor activity. Proc Natl Acad Sci U S A 1988; 85: 6934-6938.
41. Van Snick J, Goethals A, Renauld JC, et al,. Cloning and characterization of a cDNA for a new mouse T cell growth factor (P40). J Exp Med 1989; 169: 363-368. (Pubitemid 19035570)
42. Soroosh P, Doherty TA., Th9 and allergic disease. Immunology 2009; 127: 450-458.
43. Dardalhon V, Awasthi A, Kwon H, et al,. IL-4 inhibits TGF-beta-induced Foxp3+ T cells and, together with TGF-beta, generates IL-9+ IL-10+ Foxp3(-) effector T cells [published correction appears in Nat Immunol 2009;10:551:]. Nat Immunol 2008; 9: 1347-1355.
44. Veldhoen M, Uyttenhove C, van Snick J, et al,. Transforming growth factor-beta 'reprograms' the differentiation of T helper 2 cells and promotes an interleukin 9-producing subset. Nat Immunol 2008; 9: 1341-1346.
45. Schallenberg S, Tsai PY, Riewaldt J, et al,. Identification of an immediate Foxp3(-) precursor to Foxp3(+) regulatory T cells in peripheral lymphoid organs of nonmanipulated mice. J Exp Med 2010; 207: 1393-1407.
46. Hong J, Li H, Chen M, et al,. Regulatory and pro-inflammatory phenotypes of myelin basic protein-autoreactive T cells in multiple sclerosis. Int Immunol 2009; 21: 1329-1340.
47. Miyara M, Yoshioka Y, Kitoh A, et al,. Functional delineation and differentiation dynamics of human CD4+ T cells expressing the FoxP3 transcription factor. Immunity 2009; 30: 899-911.
48. Venken K, Hellings N, Liblau R, et al,. Disturbed regulatory T cell homeostasis in multiple sclerosis. Trends Mol Med 2010; 16: 58-68.
49. 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: 7602-7610.
50. Frisullo G, Nociti V, Iorio R, et al,. Regulatory T cells fail to suppress CD4T+-bet+ T cells in relapsing multiple sclerosis patients. Immunology 2009; 127: 418-428.
51. Frisullo G, Nociti V, Iorio R, et al,. CD8(+)Foxp3(+) T cells in peripheral blood of relapsing-remitting multiple sclerosis patients. Hum Immunol 2010; 71: 437-441.
52. Correale J, Villa A., Role of CD8+ CD25+ Foxp3+ regulatory T cells in multiple sclerosis. Ann Neurol 2010; 67: 625-638.
53. McGeachy MJ, Stephens LA, Anderton SM., Natural recovery and protection from autoimmune encephalomyelitis: contribution of CD4+CD25+ regulatory cells within the central nervous system. J Immunol 2005; 175: 3025-3032. (Pubitemid 41170521)
54. Feger U, Luther C, Poeschel S, et al,. Increased frequency of CD4+ CD25+ regulatory T cells in the cerebrospinal fluid but not in the blood of multiple sclerosis patients. Clin Exp Immunol 2007; 147: 412-418. (Pubitemid 46208041)
55. Korn T, Mitsdoerffer M, Croxford AL, et al,. IL-6 controls Th17 immunity in vivo by inhibiting the conversion of conventional T cells into Foxp3+ regulatory T cells. Proc Natl Acad Sci U S A 2008; 105: 18460-18465.
56. Hong J, Li N, Zhang X, et al,. Induction of CD4+CD25+ regulatory T cells by copolymer-I through activation of transcription factor Foxp3. Proc Natl Acad Sci U S A 2005; 102: 6449-6454. (Pubitemid 40617463)
57. De Andres C, Aristimuno C, de Las Heras V, et al,. Interferon beta-1a therapy enhances CD4+ regulatory T-cell function: an ex vivo and in vitro longitudinal study in relapsing-remitting multiple sclerosis. J Neuroimmunol 2007; 182: 204-211. (Pubitemid 46026708)
58. Braitch M, Harikrishnan S, Robins RA, et al,. Glucocorticoids increase CD4CD25 cell percentage and Foxp3 expression in patients with multiple sclerosis. Acta Neurol Scand 2009; 119: 239-245.
59. Lucchinetti C, Brück W, Parisi J, et al,. Heterogeneity of multiple sclerosis lesions: implications for the pathogenesis of demyelination. Ann Neurol 2000; 47: 707-717. (Pubitemid 30390191)
60. Breij EC, Brink BP, Veerhuis R, et al,. Homogeneity of active demyelinating lesions in established multiple sclerosis. Ann Neurol 2008; 63: 16-25. (Pubitemid 351240547)
61. 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: 1089-1104. (Pubitemid 47355604)
62. Hauser SL, Waubant E, Arnold DL, et al,. B-cell depletion with rituximab in relapsing-remitting multiple sclerosis. N Engl J Med 2008; 358: 676-688. (Pubitemid 351240747)
63. Sellebjerg F, Börnsen L, Khademi M, et al,. Increased cerebrospinal fluid concentrations of the chemokine CXCL13 in active MS. Neurology 2009; 73: 2003-2010.
64. Villar LM, Espiño M, Cavanillas ML, et al,. Immunological mechanisms that associate with oligoclonal IgM band synthesis in multiple sclerosis. Clin Immunol 2010; 137: 51-59.
65. Owens GP, Ritchie AM, Burgoon MP, et al,. Single-cell repertoire analysis demonstrates that clonal expansion is a prominent feature of the B cell response in multiple sclerosis cerebrospinal fluid. J Immunol 2003; 171: 2725-2733. (Pubitemid 37025586)
66. Ascherio A, Munger KL, Lennette ET, et al,. Epstein-Barr virus antibodies and risk of multiple sclerosis: a prospective study. JAMA 2001; 286: 3083-3088. (Pubitemid 34016522)
67. Pohl D, Rostasy K, Jacobi C, et al,. Intrathecal antibody production against Epstein-Barr and other neurotropic viruses in pediatric and adult onset multiple sclerosis. J Neurol 2010; 257: 212-216.
68. Levin LI, Munger KL, O'Reilly EJ, et al,. Primary infection with the Epstein-Barr virus and risk of multiple sclerosis. Ann Neurol 2010; 67: 824-830.
69. Levin LI, Munger KL, Rubertone MV, et al,. Temporal relationship between elevation of Epstein-Barr virus antibody titers and initial onset of neurological symptoms in multiple sclerosis. JAMA 2005; 293: 2496-2500. (Pubitemid 40705731)
70. De Jager PL, Simon KC, Munger KL, et al,. Integrating risk factors: HLA-DRB1*1501 and Epstein-Barr virus in multiple sclerosis. Neurology 2008; 70: 1113-1118. (Pubitemid 351464768)
71. Sundstrom P, Nystrom M, Ruuth K, et al,. Antibodies to specific EBNA-1 domains and HLA DRB1*1501 interact as risk factors for multiple sclerosis. J Neuroimmunol 2009; 215: 102-107.
72. Zivadinov R, Zorzon M, Weinstock-Guttman B, et al,. Epstein-Barr virus is associated with grey matter atrophy in multiple sclerosis. J Neurol Neurosurg Psychiatry 2009; 80: 620-625.
73. Serafini B, Severa M, Columba-Cabezas S, et al,. Epstein-Barr virus latent infection and BAFF expression in B cells in the multiple sclerosis brain: implications for viral persistence and intrathecal B-cell activation. J Neuropathol Exp Neurol 2010; 69: 677-693.
74. Samanta M, Iwakiri D, Kanda T, et al,. EB virus-encoded RNAs are recognized by RIG-I and activate signaling to induce type I IFN. EMBO J 2006; 25: 4207-4214. (Pubitemid 44435218)
75. Iwakiri D, Zhou L, Samanta M, et al,. Epstein-Barr virus (EBV)-encoded small RNA is released from EBV-infected cells and activates signaling from Toll-like receptor 3. J Exp Med 2009; 206: 2091-2099.
76. Iwakiri D, Takada K., Role of EBERs in the pathogenesis of EBV infection. Adv Cancer Res 2010; 107: 119-136.
77. Zhang X, Markovic-Plese S., Interferon beta inhibits the Th17 cell-mediated autoimmune response in patients with relapsing-remitting multiple sclerosis. Clin Neurol Neurosurg 2010; 112: 641-645.
78. Begum-Haque S, Sharma A, Christy M, et al,. Increased expression of B cell-associated regulatory cytokines by glatiramer acetate in mice with experimental autoimmune encephalomyelitis. J Neuroimmunol 2010; 219: 47-53.
79. Steinman RM, Banchereau J., Taking dendritic cells into medicine. Nature 2007; 449: 419-426. (Pubitemid 47509552)
80. Liu YJ., IPC: professional type 1 interferon-producing cells and plasmacytoid dendritic cell precursors. Annu Rev Immunol 2005; 23: 275-306.
81. Zozulya AL, Clarkson BD, Ortler S, et al,. The role of dendritic cells in CNS autoimmunity. J Mol Med 2010; 88: 535-544.
82. Menges M, Rossner S, Voigtlander C, et al,. Repetitive injections of dendritic cells matured with tumor necrosis factor alpha induce antigen-specific protection of mice from autoimmunity. J Exp Med 2002; 195: 15-21. (Pubitemid 34074492)
83. Serafini B, Rosicarelli B, Magliozzi R, et al,. Dendritic cells in multiple sclerosis lesions: maturation stage, myelin uptake, and interaction with proliferating T cells. J Neuropathol Exp Neurol 2006; 65: 124-141.
84. Karni A, Abraham M, Monsonego A, et al,. Innate immunity in multiple sclerosis: myeloid dendritic cells in secondary progressive multiple sclerosis are activated and drive a proinflammatory immune response. J Immunol 2006; 177: 4196-4202. (Pubitemid 44359955)
85. Weiner HL., A shift from adaptive to innate immunity: a potential mechanism of disease progression in multiple sclerosis. J Neurol 2008; 255 suppl 1 3-11. (Pubitemid 351341867)
86. Bartosik-Psujek H, Tabarkiewicz J, Pocinska K, et al,. Immunomodulatory effects of IFN-beta and lovastatin on immunophenotype of monocyte-derived dendritic cells in multiple sclerosis. Arch Immunol Ther Exp (Warsz) 2010; 58: 313-319.
87. Ramgolam VS, Markovic-Plese S., Interferon-beta inhibits Th17 cell differentiation in patients with multiple sclerosis. Endocr Metab Immune Disord Drug Targets 2010; 10: 161-167.
88. Ruggieri M, Pica C, Lia A, et al,. Combination treatment of glatiramer acetate and minocycline affects phenotype expression of blood monocyte-derived dendritic cells in Multiple Sclerosis patients. J Neuroimmunol 2008; 197: 140-146.
89. Dhib-Jalbut S, Chen M, Said A, et al,. Glatiramer acetate-reactive peripheral blood mononuclear cells respond to multiple myelin antigens with a Th2-biased phenotype. J Neuroimmunol 2003; 140: 163-171. (Pubitemid 36836102)
90. Weber MS, Prod'homme T, Youssef S, et al,. Type II monocytes modulate T cell-mediated central nervous system autoimmune disease. Nat Med 2007; 13: 935-943. (Pubitemid 47222047)
91. Sundqvist E, Bäärnhielm M, Alfredsson L, et al,. Confirmation of association between multiple sclerosis and CYP27B1. Eur J Hum Genet 2010; 18: 1349-1352.
92. Bartosik-Psujek H, Tabarkiewicz J, Pocinska K, et al,. Immunomodulatory effects of vitamin D on monocyte-derived dendritic cells in multiple sclerosis. Mult Scler 2010; 16: 1513-1516.
93. Fabriek BO, Van Haastert ES, Galea I, et al,. CD163-positive perivascular macrophages in the human CNS express molecules for antigen recognition and presentation. Glia 2005; 51: 297-305. (Pubitemid 41532105)
94. Van Zwam M, Huizinga R, Melief MJ, et al,. Brain antigens in functionally distinct antigen-presenting cell populations in cervical lymph nodes in MS and EAE. J Mol Med 2009; 87: 273-286.
95. Bielekova B, Catalfamo M, Reichert-Scrivner S, et al,. Regulatory CD56(bright) natural killer cells mediate immunomodulatory effects of IL-2Ralpha-targeted therapy (daclizumab) in multiple sclerosis. Proc Natl Acad Sci U S A 2006; 103: 5941-5946.
96. Dhib-Jalbut S, Marks S., Interferon-beta mechanisms of action in multiple sclerosis. Neurology 2010; 74 suppl 1 S17-S24.
97. Graber JJ, McGraw CA, Kimbrough D, et al,. Overlapping and distinct mechanisms of action of multiple sclerosis therapies. Clin Neurol Neurosurg 2010; 112: 583-591.