Animal models of Multiple Sclerosis

European Journal of Pharmacology

Volumn 759, Issue , 2015, Pages 182-191

  Procaccini, Claudio ^a   De Rosa, Veronica ^a,b   Pucino, Valentina ^a   Formisano, Luigi ^c   Matarese, Giuseppe ^d,e  

^a UNIVERSITY OF NAPLES FEDERICO II   (Italy)

^b IRCCS FONDAZIONE SANTA LUCIA   (Italy)

^c UNIVERSITY OF SANNIO   (Italy)

^d UNIVERSITY OF SALERNO   (Italy)

^e IRCCS MULTIMEDICA   (Italy)

Author keywords

EAE; Immune system; Multiple Sclerosis

Indexed keywords

ANIMAL; CARDIOVIRUS INFECTION; DISEASE MODEL; ENCEPHALOMYELITIS, AUTOIMMUNE, EXPERIMENTAL; GENETICS; HUMAN; IMMUNOLOGY; MOUSE; MULTIPLE SCLEROSIS; PATHOGENICITY; PATHOLOGY; THEILOVIRUS; TRANSGENIC MOUSE; VIROLOGY;

ANIMALS; CARDIOVIRUS INFECTIONS; DISEASE MODELS, ANIMAL; ENCEPHALOMYELITIS, AUTOIMMUNE, EXPERIMENTAL; HUMANS; MICE; MICE, TRANSGENIC; MULTIPLE SCLEROSIS; THEILOVIRUS;

EID: 84937764384     PISSN: 00142999     EISSN: 18790712     Source Type: Journal    
DOI: 10.1016/j.ejphar.2015.03.042     Document Type: Review

References (154)

1. S. Abromson-Leeman, R.T. Bronson, and M.E. Dorf Encephalitogenic T cells that stably express both T-bet and ROR-gamma t consistently produce IFN-gamma but have a spectrum of IL-17 profiles J. Neuroimmunol. 215 2009 10 24
2. K. Adlard, L. Tsaknardis, A. Beam, B.F. Bebo Jr., A.A. Vandenbark, and H. Offner Immunoregulation of encephalitogenic MBP-NAc1-11-reactive T cells by CD4+ TCR-specific T cells involves IL-4, IL-10 and IFN-gamma Autoimmunity 31 1999 237 248
3. R. Aharoni, A. Herschkovitz, R. Eilam, M. Blumberg-Hazan, M. Sela, W. Brü ck, and R. Arnon Demyelination arrest and remyelination induced by glatiramer acetate treatment of experimental autoimmune encephalomyelitis Proc. Natl. Acad. Sci. USA 105 2008 11358 11363
4. R. Aharoni, D. Teitelbaum, M. Sela, and R. Arnon Copolymer 1 induces T cells of the T helper type 2 that crossreact with myelin basic protein and suppress experimental autoimmune encephalomyelitis Proc. Natl. Acad. Sci. USA 94 1997 10821 10826
5. A.C. Anderson, R. Chandwaskar, D.H. Lee, J.M. Sullivan, A. Solomon, R. Rodriguez-Manzanet, B. Greve, R.A. Sobel, and V.K. Kuchroo A transgenic model of central nervous system autoimmunity mediated by CD4+ and CD8+ T and B cells J. Immunol. 188 2012 2084 2092
6. A. Ascherio, and K.L. Munger Environmental risk factors for multiple sclerosis. Part I: the role of infection Ann. Neurol. 61 2007 288 299
7. A. Ascherio, K.L. Munger, E.T. Lennette, D. Spiegelman, M.A. Hernan, M.J. Olek, S.E. Hankinson, and D.J. Hunter Epstein-Barr virus antibodies and risk of multiple sclerosis: a prospective study J. Am. Med. Assoc. 286 2001 3083 3088
8. S.E. Baranzini The genetics of autoimmune diseases: a networked perspective Curr. Opin. Immunol. 21 2009 596 605
9. J.L. Baron, J.A. Madri, N.H. Ruddle, G. Hashim, and C.A. Janeway Jr. Surface expression of alpha 4 integrin by CD4 T cells is required for their entryinto brain parenchyma J. Exp. Med. 177 1993 57 68
10. H. Batoulis, M.S. Recks, K. Addicks, and S. Kuerten Experimental autoimmune encephalomyelitis e achievements and prospective advances Acta Pathol. Microbiol. Immunol. Scand. 119 2011 819e30
11. B. Becher, B.G. Durell, and R.J. Noelle Experimental autoimmune encephalitis and inflammation in the absence ofinterleukin-12 J. Clin. Investig. 110 2002 493 497
12. K. Benardais, A. Kotsiari, J. Skuljec, P.N. Koutsoudaki, V. Gudi, V. Singh, F. Vulinović, T. Skripuletz, and M. Stangel Cuprizone [Bis(Cyclohexylidenehydrazide)] is selectively toxic for mature oligodendrocytes Neurotox. Res. 24 2013 244 250
13. J.L. Berard, K. Wolak, S. Fournier, and S. David Characterization of relapsing remitting and chronic forms of experimental autoimmune encephalomyelitis in C57BL/6 mice Glia 58 2010 434e45
14. E. Bettelli, M. Pagany, H.L. Weiner, C. Linington, R.A. Sobel, and V.K. Kuchroo Myelin oligodendrocyte glycoprotein-specific T cell receptor transgenic mice develop spontaneous autoimmune optic neuritis J. Exp. Med. 197 2003 1073 1081
15. E. Bettelli, B. Sullivan, S.J. Szabo, R.A. Sobel, L.H. Glimcher, and V.K. Kuchroo Loss of T-bet, but not STAT1, prevents the development of experimental autoimmune encephalomyelitis J. Exp. Med. 200 2004 79 87
16. A.J. Bieber, S. Kerr, and M. Rodriguez Efficient central nervous system remyelination requires T cells Ann. Neurol. 53 2003 680 684
17. B. Bielekova, B. Goodwin, N. Richert, I. Cortese, T. Kondo, G. Afshar, B. Gran, J. Eaton, J. Antel, J.A. Frank, H.F. McFarland, and R. Martin Encephalitogenic potential of the myelin basic protein peptide (amino acids 83- 99) in multiple sclerosis: results of a phase II clinical trial with an altered peptide ligand Nat. Med. 6 2000 1167 1175
18. B. Bielekova, N. Richert, T. Howard, A.N. Packer, G. Blevins, J. Ohayon, H.F. McFarland, C.S. Sturzebecher, and R. Martin Treatment with the phosphodiesterase type-4 inhibitor rolipram fails to inhibit blood-brain barrier disruption in multiple sclerosis Mult. Scler. 15 2009 1206 1214
19. W.F. Blakemore, and R.J. Franklin Remyelination in experimental models of toxin-induced demyelination Curr. Top. Microbiol. Immunol. 318 2008 193 212
20. B. Broux, N. Hellings, K. Venken, J.L. Rummens, K. Hensen, B. Van Wijmeersch, and P. Stinissen Haplotype 4 of the multiple sclerosis-associated interleukin-7 receptor alpha gene influences the frequency of recent thymic emigrants Genes Immun. 11 2010 326 333
21. D.C. Bullard, X. Hu, J.E. Adams, T.R. Schoeb, and S.R. Barnum p150/95 (CD11c/CD18)expression is required for the development of experimental autoimmune encephalomyelitis Am. J. Pathol. 170 2007 2001 2008
22. A.J. Coles, A. Cox, E. Le Page, J. Jones, S.A. Trip, J. Deans, S. Seaman, D.H. Miller, G. Hale, H. Waldmann, and D.A. Compston The window of therapeutic opportunity in multiple sclerosis: evidence from monoclonal antibody therapy J. Neurol. 253 2006 98 108
23. D.J. Cua, J. Sherlock, Y. Chen, C.A. Murphy, B. Joyce, B. Seymour, L. Lucian, W. To, S. Kwan, T. Churakova, S. Zurawski, M. Wiekowski, S.A. Lira, D. Gorman, R.A. Kastelein, and J.D. Sedgwick Interleukin-23 rather than interleukin-12 is the critical cytokine for autoimmune inflammation of the brain Nature 421 2003 744 748
24. M.C. Dal Canto, and H.L. Lipton Multiple sclerosis. Animal model: Theiler's virus infection in mice Am. J. Pathol. 88 1977 497 500
25. C. de Andrés, C. Aristimuño, V. de Las Heras, M.L. Martínez-Ginés, M. Bartolomé, R. Arroyo, J. Navarro, S. Giménez-Roldán, E. Fernández-Cruz, and S. Sánchez-Ramón 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. 182 2007 204 211
26. P.L. De Jager, X. Jia, J. Wang, P.I. de Bakker, L. Ottoboni, N.T. Aggarwal, L. Piccio, S. Raychaudhuri, D. Tran, C. Aubin, R. Briskin, S. Romano, International MS Genetics Consortium, S.E. Baranzini, J.L. McCauley, M.A. Pericak-Vance, J.L. Haines, R.A. Gibson, Y. Naeglin, B. Uitdehaag, P.M. Matthews, L. Kappos, C. Polman, W.L. McArdle, D.P. Strachan, D. Evans, A.H. Cross, M.J. Daly, A. Compston, S.J. Sawcer, H.L. Weiner, S.L. Hauser, D.A. Hafler, and J.R. Oksenberg Meta-analysis of genome scans and replication identify CD6, IRF8 and TNFRSF1A as new multiple sclerosis susceptibility loci Nat. Genet. 41 2009 776 782
27. P.L. De Jager, K.C. Simon, K.L. Munger, J.D. Rioux, D.A. Hafler, and A. Ascherio Integrating risk factors: HLA-DRB1∗ 1501 and Epstein-Barr virus in multiple sclerosis Neurology 70 2008 1113 1118
28. V. De Rosa, C. Procaccini, A. La Cava, P. Chieffi, G.F. Nicoletti, S. Fontana, S. Zappacosta, and G. Matarese Leptin neutralization interferes with pathogenic T cell autoreactivity in autoimmune encephalomyelitis J. Clin. Investig. 116 2006 447 455
29. T. Derfuss, K. Parikh, S. Velhin, M. Braun, E. Mathey, M. Krumbholz, T. Kümpfel, A. Moldenhauer, C. Rader, P. Sonderegger, W. Pöllmann, C. Tiefenthaller, J. Bauer, H. Lassmann, H. Wekerle, D. Karagogeos, R. Hohlfeld, C. Linington, and E. Meinl Contactin-2/TAG-1-directed autoimmunity is identified in multiple sclerosis patients and mediates gray matter pathology in animals Proc. Natl. Acad. Sci. USA 106 2009 8302 8307
30. F. Dittrich, H. Thoenen, and M. Sendtner Ciliary neurotrophic factor: pharmacokinetics and acute-phase response in rat Ann. Neurol. 35 1994 151 163
31. H.S. Domingues, M. Mues, H. Lassmann, H. Wekerle, and G. Krishnamoorthy Functional and pathogenic differences of Th1 and Th17 cells in experimental autoimmune encephalomyelitis PLoS One 5 2010 e15531
32. M. Dominguez-Villar, C.M. Baecher-Allan, and D.A. Hafler Identification of T helper type 1-like, Foxp3+ regulatory T cells inhuman autoimmune disease Nat. Med. 17 2011 673 675
33. G. Elain, K. Jeanneau, A. Rutkowska, A.K. Mir, and K.K. Dev The selective anti-IL17A monoclonal antibody secukinumab (AIN457) attenuates IL17A-induced levels of IL6 in human astrocytes Glia 62 2014 725 735
34. J.A. Encinas, L.S. Wicker, L.B. Peterson, A. Mukasa, C. Teuscher, R. Sobel, H.L. Weiner, C.E. Seidman, J.G. Seidman, and V.K. Kuchroo QTL influencing autoimmune diabetes and encephalomyelitis map to a 0.15-cM region containing Il2 Nat. Genet. 21 1999 158 160
35. I.A. Ferber, S. Brocke, C. Taylor-Edwards, W. Ridgway, C. Dinisco, L. Steinman, D. Dalton, and C.G. Fathman Mice with a disrupted IFN-gamma gene are susceptible to the induction of experimental autoimmune encephalomyelitis (EAE) J. Immunol. 156 1996 5 7
36. M.L. Ford, and B.D. Evavold Specificity, magnitude, and kinetics of MOG-specific CD8+ T cell responses during experimental autoimmune encephalomyelitis Eur. J. Immunol. 35 2005 76 85
37. J. Freund, and K. McDermott Sensitisation to horse serum by means of adjuvants Proc. Soc. Exp. Biol. 49 1942 548 553
38. J. Freund, E.R. Stern, and T.M. Pisani Isoallergic encephalomyelitis and radiculitis in guinea pigs after one injection of brain and mycobacteria in water-in-oil emulsion J. Immunol. 57 1947 179 194
39. M.A. Friese, and L. Fugger Pathogenic CD8(+) T cells in multiple sclerosis Ann. Neurol. 66 2009 132 141
40. G. Frisullo, V. Nociti, R. Iorio, A.K. Patanella, M. Caggiula, A. Marti, C. Sancricca, F. Angelucci, M. Mirabella, P.A. Tonali, and A.P. Batocchi Regulatory T cells fail to suppress CD4T+-bet+ T cells in relapsing multiple sclerosis patients Immunology 127 2009 418 428
41. E.M. Frohman, M.K. Racke, and C.S. Raine Multiple sclerosis e the plaque and its pathogenesis N. Engl. J. Med. 354 2006 942e55
42. R.S. Fujinami, A. Rosenthal, P.W. Lampert, A. Zurbriggen, and M. Yamada Survival of athymic (nu/nu) mice after Theiler's murine encephalomyelitis virus infection by passive administration of neutralizing monoclonal antibody J. Virol. 63 1989 2081 2087
43. S.J. Gerety, M.K. Rundell, M.C. Dal Canto, and S.D. Miller Class IIrestricted T cell responses in Theiler's murine encephalomyelitis virus-induced demyelinating disease. VI. Potentiation of demyelination with and characterization of an immunopathologic CD4+ T cell line specific for an immunodominant VP2 epitope J. Immunol. 152 1994 919 929
44. J. Goverman Autoimmune T cell responses in the central nervous system Nat. Rev. Immunol. 9 2009 393 407
45. J. Haas, A. Hug, A. Viehöver, B. Fritzsching, C.S. Falk, A. Filser, T. Vetter, L. Milkova, M. Korporal, B. Fritz, B. Storch-Hagenlocher, P.H. Krammer, E. Suri-Payer, and B. Wildemann Reduced suppressive effect of CD4+CD25high regulatory T cells on the T cellimmune response against myelin oligodendrocyte glycoprotein in patients with multiple sclerosis Eur. J. Immunol. 35 2005 3343 3352
46. D.A. Hafler, J.M. Slavik, D.E. Anderson, K.C. O'Connor, P. De Jager, and C. Baecher-Allan Multiple sclerosis Immunol. Rev. 204 2005 208 231
47. S.M. Hall The effect of injections of lysophosphatidyl choline into white matter of the adult mouse spinal cord J. Cell. Sci. 10 1972 535 546
48. H.P. Hartung, R. Gonsette, N. Konig, H. Kwiecinski, A. Guseo, S.P. Morrissey, H. Krapf, and T. Zwingers Mitoxantrone in multiple sclerosis study group (MIMS) mitoxantrone in progressive multiple sclerosis: a placebo-controlled, doubleblind, randomised, multicentre trial Lancet 360 2002 2018 2025
49. S.L. Hauser, A.K. Bhan, F. Gilles, M. Kemp, C. Kerr, and H.L. Weiner Immunohistochemical analysis of the cellular infiltrate in multiple sclerosis lesions Ann. Neurol. 19 1986 578 587
50. S.L. Hauser, E. Waubant, D.L. Arnold, T. Vollmer, J. Antel, R.J. Fox, A. Bar-Or, M. Panzara, N. Sarkar, S. Agarwal, A. Langer-Gould, C.H. Smith, and HERMES Trial Group B-cell depletion with rituximab in relapsing-remitting multiple sclerosis N. Engl. J. Med. 358 2008 676 688
51. R.D. Hemm, W.W. Carlton, and J.R. Welser Ultrastructural changes of cuprizone encephalopathy in mice Toxicol. Appl. Pharmacol. 18 1971 869 882
52. P. Hjelmstrom, A.E. Juedes, J. Fjell, and N.H. Ruddle B-cell-deficient mice develop experimental allergic encephalomyelitis with demyelination after myelin oligodendrocyte glycoprotein sensitization J. Immunol. 161 1998 4480 4483
53. H.H. Hofstetter, S.M. Ibrahim, D. Koczan, N. Kruse, A. Weishaupt, K.V. Toyka, and R. Gold Therapeutic efficacy of IL-17 neutralization in murine experimental autoimmune encephalomyelitis Cell. Immunol. 237 2005 123 130
54. Y. Hu, N. Ota, I. Peng, C.J. Refino, D.M. Danilenko, P. Caplazi, and W. Ouyang IL-17RC is required for IL-17A- and IL-17F-dependent signaling and the pathogenesis of experimental autoimmune encephalomyelitis J. Immunol. 184 2010 4307 4316
55. M. Jacobsen, S. Cepok, E. Quak, M. Happel, R. Gaber, A. Ziegler, S. Schock, W.H. Oertel, N. Sommer, and B. Hemmer Oligoclonal expansion of memory CD8+ T cells in cerebrospinal fluid from multiple sclerosis patients Brain 125 2002 538 550
56. A. Jäger, V. Dardalhon, R.A. Sobel, E. Bettelli, and V.K. Kuchroo Th1, Th17, and Th9 effector cells induce experimental autoimmune encephalomyelitis with different pathological phenotypes J. Immunol. 183 2009 7169 7177
57. N.D. Jeffery, and W.F. Blakemore Remyelination of mouse spinal cord axons demyelinated by local injection of lysolecithin J. Neurocytol. 24 1995 775 781
58. A. Junker, J. Ivanidze, J. Malotka, I. Eiglmeier, H. Lassmann, H. Wekerle, E. Meinl, R. Hohlfeld, and K.l. Dornmair Multiple sclerosis: T-cell receptor expression in distinct brain regions Brain 130 2007 2789 2799
59. E.A. Kabat, A. Wolf, and A.E. Bezer The rapid production of acute disseminated encephalomyelitis in rhesus monkeys by injection of heterologous and homologous brain tissue with adjuvants J. Exp. Med. 85 1947 117 130
60. L. Kappos, G. Comi, H. Panitch, J. Oger, J. Antel, P. Conlon, and L. Steinman Induction of a nonencephalitogenic type 2T helper-cell autoimmune response in multiple sclerosis after administration of an altered peptide ligand in a placebo-controlled, randomized phase II trial. The Altered Peptide Ligand in Relapsing MS Study Group Nat. Med. 6 2000 1176 1182
61. H. Kebir, I. Ifergan, J.I. Alvarez, M. Bernard, J. Poirier, N. Arbour, P. Duquette, and A. Prat Preferential recruitment of interferon-gamma-expressing TH17 cells in multiple sclerosis Ann. Neurol. 66 2009 390 402
62. H. Kebir, K. Kreymborg, I. Ifergan, A. Dodelet-Devillers, R. Cayrol, M. Bernard, F. Giuliani, N. Arbour, B. Becher, and A. Prat Human TH17 lymphocytes promote blood-brain barrier disruption and central nervous system inflammation Nat. Med. 13 2007 1173 1175
63. B.C. Kieseier, and H.P. Hartung Current disease-modifying therapies in multiple sclerosis Semin. Neurol. 23 2003 133 146
64. M. Kleinewietfeld, and D.A. Hafler Regulatory T cells in autoimmune neuroinflammation Immunol. Rev. 259 2014 231 244
65. D.R. Koh, W.P. Fung-Leung, A. Ho, D. Gray, H. Acha-Orbea, and T.W. Mak Less mortalitybut more relapses in experimental allergic encephalomyelitis in CD8-/- mice Science 256 1992 1210 1213
66. A.P. Kohm, P.A. Carpentier, H.A. Anger, and S.D. Miller Cutting edge: CD4+CD25+ regulatory T cells suppress antigen-specificautoreactive immune responses and central nervous system inflammation during activeexperimental autoimmune encephalomyelitis J. Immunol. 169 2002 4712 4716
67. Y. Komiyama, S. Nakae, T. Matsuki, A. Nambu, H. Ishigame, S. Kakuta, K. Sudo, and Y. Iwakura IL-17 plays an important role in the development of experimental autoimmune encephalomyelitis J. Immunol. 177 2006 566 573
68. S. Komoly, M.D. Jeyasingham, O.E. Pratt, and P.L. Lantos Decrease in oligodendrocyte carbonic anhydrase activity preceding myelin degeneration in cuprizone induced demyelination J. Neurol. Sci. 79 1987 141 148
69. T. Korn, J. Reddy, W. Gao, E. Bettelli, A. Awasthi, TR. Petersen, B.T. Bäckström, R.A. Sobel, K.W. Wucherpfennig, T.B. Strom, M. Oukka, and V.K. Kuchroo Myelin-specific regulatory T cells accumulate in the CNS but fail to control autoimmune inflammation Nat. Med. 13 2007 423 431
70. M. Korporal, J. Haas, B. Balint, B. Fritzsching, A. Schwarz, S. Moeller, B. Fritz, E. Suri-Payer, and B. Wildemann Interferon beta-induced restoration of regulatory T-cell function in multiple sclerosis is prompted by an increase in newly generated naive regulatory T cells Arch. Neurol. 65 2008 1434 1439
71. G. Krishnamoorthy, A. Saxena, L.T. Mars, H.S. Domingues, R. Mentele, A. Ben-Nun, H. Lassmann, K. Dornmair, F.C. Kurschus, R.S. Liblau, and H. Wekerle Myelin-specific T cells also recognize neuronal autoantigen in a transgenic mouse model of multiple sclerosis Nat. Med. 15 2009 626 632
72. M.A. Kroenke, T.J. Carlson, A.V. Andjelkovic, and B.M. Segal 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 2008 1535 1541
73. F.C. Kurschus, A.L. Croxford, A.P. Heinen, S. Wörtge, D. Ielo, and A. Waisman Genetic proof for the transient nature of the Th17 phenotype Eur. J. Immunol. 40 2010 3336 3346
74. J.F. Kurtzke Epidemiologic contributions to multiple sclerosis: an overview Neurology 30 1980 61 79
75. C.L. Langrish, Y. Chen, W.M. Blumenschein, J. Mattson, B. Basham, J.D. Sedgwick, T. McClanahan, R.A. Kastelein, and D.J. Cua IL-23 drives a pathogenic T cell population that induces autoimmune inflammation J. Exp. Med. 201 2005 233 240
76. J.E. Libbey, and R.S. Fujinami Viral demyelinating disease in experimental animals RM. Herndon, Multiple Sclerosis: Immunology, Pathology and Pathophysiology 2003 Demos New York 125 133
77. J.W. Lindsey, S. Hodgkinson, R. Mehta, R.C. Siegel, D.J. Mitchell, M. Lim, C. Piercy, T. Tram, L. Dorfman, and D. Enzmann Phase 1 clinical trial of chimeric monoclonal anti-CD4 antibody in multiple sclerosis Neurology 44 1994 413 419
78. H. Link, J.B. Sun, Z. Wang, Z. Xu, A. Löve, S. Fredrikson, and T. Olsson Virus-reactive and autoreactive T cells are accumulated in cerebro spinal fluid in multiple sclerosis J. Neuroimmunol. 38 1992 63 73
79. H.L. Lipton, G. Twaddle, and M.L. Jelachich The predominant virus antigen burden is present in macrophages in Theiler's murine encephalomyelitis virus-induced demyelinating disease J. Virol. 69 1995 2525 2533
80. M.M. Lipton, and J. Freund Encephalomyelitis in the rat following intracutaneousinjection of central nervous system tissue with adjuvant Proc. Soc. Exp. Biol. Med. 81 1952 260 261
81. T. Litzenburger, R. Fassler, J. Bauer, H. Lassmann, C. Linington, H. Wekerle, and A. Iglesias B lymphocytes producing demyelinating autoantibodies: development and function in gene-targeted transgenic mice J. Exp. Med. 188 1998 169 180
82. L. Liu, A. Belkadi, L. Darnall, T. Hu, C. Drescher, A.C. Cotleur, D. Padovani-Claudio, T. He, K. Choi, T.E. Lane, R.H. Miller, and R.M. Ransohoff CXCR2-positive neutrophils are essential for cuprizone-induced demyelination: relevance to multiple sclerosis Nat. Neurosci. 13 2010 319 326
83. C. Lock, G. Hermans, R. Pedotti, A. Brendolan, E. Schadt, H. Garren, A. Langer-Gould, S. Strober, B. Cannella, J. Allard, P. Klonowski, A. Austin, N. Lad, N. Kaminski, S.J. Galli, J.R. Oksenberg, C.S. Raine, R. Heller, and L. Steinman Gene-microarray analysis of multiple sclerosis lesions yields new targets validated in autoimmune encephalomyelitis Nat. Med. 8 2002 500 508
84. E.E. Longbrake, and M.K. Racke Why did IL-12/IL-23 antibody therapy fail in multiple sclerosis? Expert Rev. Neurother. 9 2009 319 321
85. C. Lucchinetti, W. Bruck, J. Parisi, B. Scheithauer, M. Rodriguez, and H. Lassmann Heterogeneity of multiple sclerosis lesions: implications for the pathogenesis of demyelination Ann. Neurol. 47 2000 707 717
86. J.A. Lyons, M. San, M.P. Happ, and A.H. Cross B cells are critical to induction of experimental allergic encephalomyelitis by protein but not by a short encephalitogenic peptide Eur. J. Immunol. 29 1999 3432 3439
87. L.T. Mars, P. Saikali, R.S. Liblau, and N. Arbour Contribution of CD8 T lymphocytes to the immuno-pathogenesis of multiplesclerosis and its animal models Biochim. Biophys. Acta 1812 2011 151 161
88. N.E. Martinez, F. Karlsson, F. Sato, E. Kawai, S. Omura, A. Minagar, M.B. Grisham, and I. Tsunoda Protective and detrimental roles for regulatory T cells in a viral model for multiple sclerosis Brain Pathol. 24 2014 436 451
89. G. Matarese, P.B. Carrieri, A. La Cava, F. Perna, V. Sanna, V. De Rosa, D. Aufiero, S. Fontana, and S. Zappacosta Leptin increase in multiple sclerosis associates with reduced number of CD4+CD25+ regulatory T cells Proc. Natl. Acad. Sci. USA 102 2005 5150 5155
90. E.K. Mathey, T. Derfuss, M.K. Storch, K.R. Williams, K. Hales, D.R. Woolley, A. Al-Hayani, S.N. Davies, M.N. Rasband, T. Olsson, A. Moldenhauer, S. Velhin, R. Hohlfeld, E. Meinl, and C. Linington Neurofascin as a novel target for autoantibody-mediated axonal injury J. Exp. Med. 204 2007 2363 2372
91. G.K. Matsushima, and P. Morell The neurotoxicant, cuprizone, as a model to study demyelination and remyelination in the central nervous system Brain Pathol. 11 2001 107 116
92. D.E. McFarlin, and H.F. McFarland Multiple sclerosis (first of two parts) N. Engl. J. Med. 307 1982 1183 1188
93. B.L. McRae, M.K. Kennedy, L.J. Tan, M.C. Dal Canto, K.S. Picha, and S.D. Miller Induction of active and adoptive relapsing experimental autoimmune encephalomyelitis (EAE) using an encephalitogenic epitope of proteolipid protein J. Neuroimmunol. 38 1992 229e40
94. B.L. McRae, C.L. Vanderlugt, M.C. Dal Canto, and S.D. Miller Functional evidence for epitope spreading in the relapsing pathology of experimental autoimmune encephalomyelitis J. Exp. Med. 182 1995 75e85
95. E. Meinl, T. Derfuss, M. Krumbholz, A.K. Pröbstel, and R. Hohlfeld Humoral autoimmunity in multiple sclerosis J. Neurol. Sci. 306 2011 180 182
96. I. Mendel, Kerlero, N. de Rosbo, and A. Ben-Nun A myelin oligodendrocyte glycoprotein peptide induces typical chronic experimental autoimmune encephalomyelitis in H-2b mice: fine specificity and T cell receptor V beta expression of encephalitogenic T cells Eur. J. Immunol. 25 1995 1951 1959
97. L. Mestre, F. Docagne, F. Correa, F. Loría, M. Hernangómez, J. Borrell, and C. Guaza A cannabinoid agonist interferes with the progression of a chronic model of multiple sclerosis by downregulating adhesion molecules Mol. Cell. Neurosci. 40 2009 258 266
98. E. Mix, H. Meyer-Rienecker, H.P. Hartung, and U.K. Zettl Animal models of multiple sclerosis: potentials and limitations Prog. Neurobiol. 92 2010 386 404
99. F. Miyagawa, J. Gutermuth, H. Zhang, and S.I. Katz The use of mouse models to better understand mechanisms of autoimmunity and tolerance J. Autoimmun. 35 2010 192 198
100. J. Monteiro, R. Hingorani, R. Pergolizzi, B. Apatoff, and P.K. Gregersen Clonal dominance of CD8+ T-cell in multiple sclerosis Ann. N. Y. Acad. Sci. 756 1995 310 312
101. I.M. Morgan Allergic encephalomyelitis in monkeys in response to injection of normal monkey nervous tissue J. Exp. Med. 85 1947 131 140
102. S.P. Morrissey, H. Stodal, U. Zettl, C. Simonis, S. Jung, R. Kiefer, H. Lassmann, H.P. Hartung, A. Haase, and K.V. Toyka In vivo MRI and its histological correlates in acute adoptive transfer experimental allergic encephalomyelitis. Quantification of inflammation and oedema Brain 119 1996 239 248
103. J.J. Munoz, C.C. Bernard, and I.R. Mackay Elicitation of experimental allergic encephalomyelitis (EAE) in mice with the aid of pertussigen Cell. Immunol. 83 1984 92 100
104. P.D. Murray, K.D. Pavelko, J. Leibowitz, X. Lin, and M. Rodriguez CD4+ and CD8+ T cells make discrete contributions to demyelination and neurologic disease in a viral model of multiple sclerosis J. Virol. 72 1998 7320 7329
105. O. Neuhaus, H. Wiendl, B.C. Kieseier, J.J. Archelos, B. Hemmer, O. Stuve, and H.P. Hartung Multiple sclerosis: mitoxantrone promotes differential effects in immunocompetent cells in vitro J. Neuroimmunol. 168 2005 128 137
106. M.K. Njenga, C. Marques, and M. Rodriguez The role of cellular immune response in Theiler's virus induced central nervous system demyelination J. Neuroimmunol. 147 2004 73 77
107. J.H. Noseworthy, C. Lucchinetti, M. Rodriguez, and B.G. Weinshenker Multiple sclerosis N. Engl. J. Med. 343 2000 938 952
108. P.K. Olitzky, and R.H. Yager Experimental disseminated encephalomyelitis in white mice J. Exp. Med. 90 1949 213 224
109. A.R. Oliver, G.M. Lyon, and N.H. Ruddle Rat and human myelin oligodendrocyte glycoproteins induce experimental autoimmune encephalomyelitis by different mechanisms in C57BL/6 mice J. Immunol. 171 2003 462 468
110. J.K. Olson, A.M. Girvin, and S.D. Miller Direct activation of innate and antigen-presenting functions of microglia following infection with Theiler's virus J. Virol. 75 2001 9780 9789
111. G.P. Owens, M.P. Burgoon, J. Anthony, B.K. Kleinschmidt-DeMasters, and D.H. Gilden The immunoglobulin G heavy chain repertoire in multiple sclerosis plaques is distinct from the heavy chain repertoire in peripheral blood lymphocytes Clin. Immunol. 98 2001 258 263
112. T. Owens Animal models for multiple sclerosis Adv. Neurol. 98 2006 77 89
113. A.R. Pachner Experimental models of multiple sclerosis Curr. Opin. Neurol. 24 2011 291 299
114. H.S. Panitch, R.L. Hirsch, J. Schindler, and K.P. Johnson Treatment of multiple sclerosis with gamma interferon: exacerbations associated with activation of the immune system Neurology 37 1987 1097 1102
115. A. Peters, Y. Lee, and V.K. Kuchroo The many faces of Th17 cells Curr. Opin. Immunol. 23 2011 702 706
116. C.H. Polman, P.W. O'Connor, E. Havrdova, M. Hutchinson, L. Kappos, D.H. Miller, J.T. Phillips, F.D. Lublin, G. Giovannoni, A. Wajgt, M. Toal, F. Lynn, M.A. Panzara, and A.W. Sandrock AFFIRM Investigators. A randomized, placebo-controlled trial of natalizumab for relapsing multiple sclerosis N. Engl. J. Med. 354 2006 899 910
117. C.M. Poser Pathogenesis of multiple sclerosis. A critical reappraisal Acta Neuropathol. 71 1986 1 10
118. M.K. Racke, A.E. Lovett-Racke, and N.J. Karandikar The mechanism of action of glatiramer acetate treatment in multiple sclerosis Neurology 74 Suppl. 1 2010 S25 S30
119. M. Rangachari, C. Zhu, K. Sakuishi, S. Xiao, J. Karman, and A. Chen Bat3 promotes T cell responses and autoimmunity by repressing Tim-3-mediated cell death and exhaustion Nat. Med. 18 2012 1394e400
120. J. Reddy, Z. Illes, X. Zhang, J. Encinas, J. Pyrdol, L. Nicholson, R.A. Sobel, K.W. Wucherpfennig, and V.K. Kuchroo Myelin proteolipid protein-specific CD4+CD25+ regulatory cells mediate genetic resistance to experimental autoimmune encephalomyelitis Proc. Natl. Acad. Sci. USA 101 2004 15434 15439
121. S.C. Ridge, A.E. Sloboda, R.A. McReynolds, S. Levine, A.L. Oronsky, and S.S. Kerwar Suppression of experimental allergic encephalomyelitis by mitoxantrone Clin. Immunol. Immunopathol. 35 1985 35 42
122. G.P. Rice, H.P. Hartung, and P.A. Calabresi Anti-alpha 4 integrin therapy for multiple sclerosis: mechanisms and rationale Neurology 64 2005 1336 1342
123. T.M. Rivers, D.H. Sprunt, and G.P. Berry Observations on attempts to produceacute disseminated encephalomyelitis in monkeys J. Exp. Med. 58 1933 39 53
124. M. Rodriguez, and J. Quddus Effect of cyclosporin A, silica quartz dust, and protease inhibitors on virus-induced demyelination J. Neuroimmunol. 13 1986 159 174
125. C.P. Rossi, M. Delcroix, I. Huitinga, A. McAllister, N. van Rooijen, E. Claassen, and M. Brahic Role of macrophages during Theiler's virus infection J. Virol. 71 1997 3336 3340
126. V. Sanna, A. Di Giacomo, A. La Cava, R.I. Lechler, S. Fontana, S. Zappacosta, and G. Matarese Leptin surge precedes onset of autoimmune encephalomyelitis and correlates with development of pathogenic T cell responses J. Clin. Investig. 111 2003 241 250
127. B.M. Segal, and E.M. Shevach IL-12 unmasks latent autoimmune disease in resistant mice J. Exp. Med. 184 1996 771 775
128. S.A. Shields, J.M. Gilson, W.F. Blakemore, and R.J. Franklin Remyelination occurs as extensively but more slowly in old rats compared to young rats following gliotoxin-induced CNS demyelination Glia 28 1999 77 83
129. M. Sospedra, and R. Martin Immunology of multiple sclerosis Annu. Rev. Immunol. 23 2005 683 747
130. S. Sriram, and I. Steiner Experimental allergic encephalomyelitis: a misleading model of multiple sclerosis Ann. Neurol. 58 2005 939 945
131. L. Steinman, and S.S. Zamvil How to successfully apply animal studies in experimental allergic encephalomyelitis to research on multiple sclerosis Ann. Neurol. 60 2006 12 21
132. I.M. Stromnes, L.M. Cerretti, D. Liggitt, R.A. Harris, and J.M. Goverman Differential regulation of central nervous system autoimmunity by T(H)1 and T(H)17 cells Nat. Med. 14 2008 337 342
133. K. Suzuki Gianth epatic mitochondria: production in mice fed with cuprizone Science 163 1969 81 82
134. S.M. Tompkins, J. Padilla, M.C. Dal Canto, J.P. Ting, L. Van Kaer, and S.D. Miller De novo central nervous system processing of myelin antigen is required for the initiation of experimental autoimmune encephalomyelitis J. Immunol. 168 2002 4173e83
135. U. Traugott, and P. Lebon Multiple sclerosis: involvement of interferons in lesion pathogenesis Ann. Neurol. 24 1988 243 251
136. I. Tsunoda, and R.S. Fujinami Neuropathogenesis of Theiler's murine encephalomyelitis virus infection, an animal model for multiple sclerosis J. Neuroimmune Pharmacol. 5 2010 355 369
137. I. Tsunoda, Y. Iwasaki, H. Terunuma, K. Sako, and Y. Ohara A comparative study of acute and chronic diseases induced by two subgroups of Theiler's murine encephalomyelitis virus Acta Neuropathol. 91 1996 595 602
138. I. Tsunoda, L.-Q. Kuang, and R.S. Fujinami Induction of autoreactive CD8+ cytotoxic T cells during Theiler's murine encephalomyelitis virus infection: implications for autoimmunity J. Virol. 76 2002 12834 12844
139. I. Tsunoda, L-Q. Kuang, J.E. Libbey, and R.S. Fujinami Axonal injury heralds virus-induced demyelination Am. J. Pathol. 162 2003 1259 1269
140. I. Tsunoda, J.E. Libbey, and R.S. Fujinami TGF-β1 suppresses T cell infiltration and VP2 puff B mutation enhances apoptosis in acute polioencephalitis induced by Theiler's virus J. Neuroimmunol. 190 2007 80 89
141. I. Tsunoda, T. Tanaka, Y. Saijoh, and R.S. Fujinami Targeting inflammatory demyelinating lesions to sites of Wallerian degeneration Am. J. Pathol. 171 2007 1563 1575
142. V.K. Tuohy, Z. Lu, R.A. Sobel, R.A. Laursen, and M.B. Lees Identification of an encephalitogenic determinant of myelin proteolipid protein for SJL mice J. Immunol. 142 1989 1523e7
143. D.R. Ure, and M. Rodriguez Histopathology in the Theiler's virus model of demyelination E. Lavi, C.S. Constantinescu, Experimental Models of Multiple Sclerosis 2005 Springer New York 579 591
144. B.W. van Oosten, M. Lai, S. Hodgkinson, F. Barkhof, D.H. Miller, I.F. Moseley, A.J. Thompson, P. Rudge, A. McDougall, J.G. McLeod, H.J. Adèr, and C.H. Polman Treatment of multiple sclerosis with the monoclonal anti-CD4 antibody cMT412: results of a randomized, double-blind, placebocontrolled, MR-monitored phase II trial Neurology 49 1997 351 357
145. V. Viglietta, C. Baecher-Allan, H.L. Weiner, and D.A. Hafler Loss of functional suppression by CD4+CD25+ regulatory T cells in patientswith multiple sclerosis J. Exp. Med. 199 2004 971 979
146. T. Vollmer, T. Stewart, and N. Baxter Mitoxantrone and cytotoxic drugs mechanisms of action Neurology 74 Suppl. 1 2010 S41 S46
147. A.K. Wensky, G.C. Furtado, M.C. Marcondes, S. Chen, D. Manfra, S.A. Lira, D. Zagzag, and J.J. Lafaille IFN-gamma determines distinct clinical outcomes in autoimmune encephalomyelitis J. Immunol. 174 2005 1416 1423
148. R.H. Whitham, D.N. Bourdette, G.A. Hashim, R.M. Herndon, R.C. Ilg, A.A. Vandenbark, and H. Offner Lymphocytes from SJL/J mice immunized with spinal cord respond selectively to a peptide of proteolipid protein and transfer relapsing demyelinating experimental autoimmune encephalomyelitis J. Immunol. 146 1991 101 107
149. S.D. Wolf, B.N. Dittel, F. Hardardottir, and C.A. Janeway Jr. Experimental autoimmune encephalomyelitis induction in genetically B cell-deficient mice J. Exp. Med. 184 1996 2271 2278
150. M.N. Woodroofe, A.S. Bellamy, M. Feldmann, A.N. Davison, and ML. Cuzner Immunocytochemical characterisation of the immune reaction in the central nervous system in multiple sclerosis. Possible role for microglia in lesion growth J. Neurol. Sci. 74 1986 135 152
151. T.A. Yednock, C. Cannon, L.C. Fritz, F. Sanchez-Madrid, L. Steinman, and N. Karin Prevention of experimental autoimmune encephalomyelitis by antibodies against alpha 4 beta 1 integrin Nature 356 1992 63 66
152. S. Zamvil, P. Nelson, J. Trotter, D. Mitchell, R. Knobler, R. Fritz, and L. Steinman T-cell clonesspecific for myelin basic protein induce chronic relapsing paralysis and demyelination Nature 317 1985 355 358
153. L.A. Zenewicz, C. Abraham, R.A. Flavell, and J.H. Cho Unraveling the genetics of autoimmunity Cell 140 2010 791 797
154. X. Zhang, D.N. Koldzic, L. Izikson, J. Reddy, R.F. Nazareno, S. Sakaguchi, V.K. Kuchroo, and H.L. Weiner IL-10 is involved in the suppression of experimental autoimmune encephalomyelitis by CD25+CD4+ regulatory T cells Int. Immunol. 16 2004 249 256