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The origin and application of experimental autoimmune encephalomyelitis

Abstract

Experimental autoimmune encephalomyelitis (EAE) is a model of the neuroimmune system responding to priming with central nervous system (CNS)-restricted antigens. It is an excellent model of post-vaccinal encephalitis and a useful model of many aspects of multiple sclerosis. EAE has been established in numerous species and is induced by priming with a large number of CNS-derived antigens. As a consequence, the pathogenesis, pathology and clinical signs vary significantly between experimental protocols. As I describe in this Timeline article, the reductionist approach taken in some lines of investigation of EAE resulted in a reliance on results obtained under a narrow range of conditions. Although such studies made important contributions to our molecular understanding of inflammation, T-cell activation, and MHC restriction, they did not advance as effectively our knowledge of the polyantigenic responses that usually occur in CNS immunopathology and autoimmunity.

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Figure 1: Louis Pasteur in his laboratory in Paris, France.
Figure 2: Evidence of an immune response in the central nervous system of animals with experimental autoimmune encephalomyelitis (EAE).

References

  1. Gold, R., Linington, C. & Lassmann, H. Understanding pathogenesis and therapy of multiple sclerosis via animal models: 70 years of merits and culprits in experimental autoimmune encephalomyelitis research. Brain 129, 1953–1971 (2006).

    Article  PubMed  Google Scholar 

  2. Sriram, S. & Steiner, I. Experimental allergic encephalomyelitis: a misleading model of multiple sclerosis. Ann. Neurol. 58, 939–945 (2005).

    Article  CAS  PubMed  Google Scholar 

  3. Stuart, G. & Krikorian, K. S. The neuro-paralytic accidents of anti-rabies treatment. Ann. Trop. Med. 22, 327–377 (1928).

    Article  Google Scholar 

  4. Balaguer, D. D. G. Un caso de rabia paralítica. Gaceta Médica Catalana 11, 45–57 (1888)(in Spanish).

    Google Scholar 

  5. Bassoe, P. & Grinker, R. R. Human rabies and rabies vaccine encephalomyelitis. Arch. Neurol. Psych. 4, 1138–1160 (1930).

    Article  Google Scholar 

  6. Koritschoner, R. & Schweinburg, F. Klinisch und experimentelle beobachtungen über Lähmungen nach Wutschutzimpfung. Z. Immunitats Forsh 42, 217–283 (1925)(in German).

    Google Scholar 

  7. Stuart, G. & Krikorian, K. S. A fatal neuro-paralytic accident of antirabies treatment. Lancet 1, 1123–1125 (1930).

    Article  Google Scholar 

  8. Rivers, T. M., Sprunt, D. H. & Berry, G. P. Observations on attempts to produce acute disseminated encephalomyelitis in monkeys. J. Exp. Med. 58, 39–53 (1933).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Rivers, T. M. & Schwentker, F. F. Encephalomyelitis accompanied by myelin destruction experimentally produced in monkeys. J. Exp. Med. 61, 689–702 (1935).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Schwentker, F. F. & Rivers, T. M. The antibody reseponse of rabbits to injection of emulsions and extracts of homologous brain. J. Exp. Med. 60, 559–574 (1934).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Freund, J. & McDermott, K. Sensitisation to horse serum by means of adjuvants. Proc. Soc. Exp. Biol. 49, 548–553 (1942).

    Article  CAS  Google Scholar 

  12. Kabat, E. A., Wolf, A. & Bezer, A. E. The rapid production of acute disseminated encephalomyelitis in rhesus monkeys by injection of heterologous and homologous brain tissue with adjuvants. J. Exp. Med. 85, 117–130 (1947).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Morgan, I. M. Allergic encephalomyelitis in monkeys in response to injection of normal monkey nervous tissue. J. Exp. Med. 85, 131–140 (1947).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Freund, J., Stern, E. R. & Pisini, T. M. Isoallergic encephalomyelitis and radiculitis in guinea pigs after one injection of brain and mycobacteria in water-in-oil emulsion. J. Immunol. 57, 179–194 (1947).

    CAS  PubMed  Google Scholar 

  15. Wolf, A., Kabat, E. A. & Bezer, A. E. The pathology of acute disseminated encephalomyelitis produced experimentally in the rhesus monkey and its resemblance to human demyelinating disease. J. Neuropath. Exp. Neurol. 6, 333–357 (1947).

    Article  CAS  PubMed  Google Scholar 

  16. Morrison, L. R. Disseminated encephalomyelitis experimentally produced by the use of homologous antigen. Arch. Neurol. Psychiat. 58, 391–416 (1947).

    Article  CAS  PubMed  Google Scholar 

  17. Lumsden, C. E. Experimental allergic encephalomyelitis II — on the nature of the encephalitogenic agent. Brain 27, 517–537 (1949).

    Article  Google Scholar 

  18. Olitsky, P. K. & Yager, R. H. Experimental disseminated encephalomyelitis in white mice. J. Exp. Med. 90, 213–223 (1949).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Lipton, M. M. & Freund, J. Encephalomyelitis in the rat following intracutaneous injection of central nervous system tissue with adjuvant. Proc. Soc. Exp. Biol. NY 81, 260–261 (1952).

    Article  CAS  Google Scholar 

  20. Tal, C., Laufer, A. & Behar, A. J. An experimental demyelinative disease in the Syrian hamster. Br. J. Exp. Pathol. 39, 158–164 (1958).

    CAS  PubMed  PubMed Central  Google Scholar 

  21. Thomas, L., Paterson, P. Y. & Smithwick, B. Acute disseminated encephalomyelitis following immunization with homologous brain extracts: I. Studies on the role of a circulating antibody in the production of the condition in dogs. J. Exp. Med. 92, 133–152 (1950).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Innes, J. R. M. Experimental allergic encephalitis: attempts to produce the disease in sheep and goats. J. Comp. Path. 61, 241–250 (1951).

    Article  CAS  PubMed  Google Scholar 

  23. Genain, C. P. et al. Antibody facilitation of multiple sclerosis-like lesions in a nonhuman primate. J. Clin. Invest. 96, 2966–2974 (1995).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Ranzenhofer, E. R., Lipton, M. M. & Steigman, A. J. Effect of homologous spinal cord in Freund's adjuvant on cockerel comb, testicular and body growth. Proc. Soc. Exp. Biol. NY 99, 280–282 (1958).

    Article  CAS  Google Scholar 

  25. Adams, R. D. & Kubik, C. S. The morbid anatomy of the demyelinative diseases. Am. J. Med. 12, 510–546 (1952).

    Article  CAS  PubMed  Google Scholar 

  26. Ferraro, A. Pathology of demyelinating diseases as an allergic reaction of the brain. Arch. Neurol. Psych. 4, 443–483 (1944).

    Article  Google Scholar 

  27. Steinman, L. & Zamvil, S. S. How to successfully apply animal studies in experimental allergic encephalomyelitis to research on multiple sclerosis. Ann. Neurol. 60, 12–21 (2006).

    Article  CAS  PubMed  Google Scholar 

  28. Teitelbaum, D., Meshorer, A., Hirshfeld, T., Arnon, R. & Sela, M. Suppression of experimental allergic encephalomyelitis by a synthetic polypeptide. Eur. J. Immunol. 1, 242–248 (1971).

    Article  CAS  PubMed  Google Scholar 

  29. Lublin, F. D., Lavasa, M., Viti, C. & Knobler, R. L. Suppression of acute and relapsing experimental allergic encephalomyelitis with mitoxantrone. Clin. Immunol. Immunopathol. 45, 122–128 (1987).

    Article  CAS  PubMed  Google Scholar 

  30. Yednock, T. A. et al. Prevention of experimental autoimmune encephalomyelitis by antibodies against α4β1 integrin. Nature 356, 63–66 (1992).

    Article  CAS  PubMed  Google Scholar 

  31. Langer-Gould, A., Atlas, S. W., Green, A. J., Bollen, A. W. & Pelletier, D. Progressive multifocal leukoencephalopathy in a patient treated with natalizumab. N. Engl. J. Med. 353, 375–381 (2005).

    Article  CAS  PubMed  Google Scholar 

  32. Bielekova, B. et al. 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. Nature Med. 6, 1167–1175 (2000).

    Article  CAS  PubMed  Google Scholar 

  33. van Oosten, B. W. et al. Increased MRI activity and immune activation in two multiple sclerosis patients treated with the monoclonal anti-tumor necrosis factor antibody cA2. Neurology 47, 1531–1534 (1996).

    Article  CAS  PubMed  Google Scholar 

  34. Waksman, B. H., Porter, H., Lees, M. D., Adams, R. D. & Folch, J. A study of the chemical nature of components of bovine white matter effective in producing allergic encephalomyelitis in the rabbit. J. Exp. Med. 100, 451–471 (1954).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. Ferraro, A. & Roizin, L. Production of experimental encephalomyelitis with calcium acetate compound extracted from brain tissue. J. Neuropath. Exp. Neurol. 10, 394–407 (1951).

    Article  CAS  Google Scholar 

  36. Laatsch, R. H., Kies, M. W., Gordon, S. & Alvord, E. C. Jr. The encephalomyelitic activity of myelin isolated by ultracentrifugation. J. Exp. Med. 115, 777–788 (1962).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. Einstein, E. R., Robertson, D. M., DiCaprio, J. M. & Moore, W. The isolation from bovine spinal cord of a homogeneous protein with encephalitogenic activity. J. Neurochem. 9, 353–361 (1962).

    Article  CAS  PubMed  Google Scholar 

  38. Kibler, R. F. et al. Immune response of Lewis rats to peptide C1 (residues 68–88) of guinea pig and rat myelin basic proteins. J. Exp. Med. 146, 1323–1331 (1977).

    Article  CAS  PubMed  Google Scholar 

  39. Fritz, R. B., Chou, C. H. & McFarlin, D. E. Induction of experimental allergic encephalomyelitis in PL/J and (SJL/J × PL/J)F1 mice by myelin basic protein and its peptides: localization of a second encephalitogenic determinant. J. Immunol. 130, 191–194 (1983).

    CAS  PubMed  Google Scholar 

  40. Fritz, R. B., Skeen, M. J., Chou, C. H., Garcia, M. & Egorov, I. K. Major histocompatibility complex-linked control of the murine immune response to myelin basic protein. J. Immunol. 134, 2328–2332 (1985).

    CAS  PubMed  Google Scholar 

  41. Zamvil, S. S. et al. T-cell epitope of the autoantigen myelin basic protein that induces encephalomyelitis. Nature 324, 258–260 (1986).

    Article  CAS  PubMed  Google Scholar 

  42. Zamvil, S. S. et al. Predominant expression of a T cell receptor Vβ gene subfamily in autoimmune encephalomyelitis. J. Exp. Med. 167, 1586–1596 (1988).

    Article  CAS  PubMed  Google Scholar 

  43. Acha-Orbea, H. et al. Limited heterogeneity of T cell receptors from lymphocytes mediating autoimmune encephalomyelitis allows specific immune intervention. Cell 54, 263–273 (1988).

    Article  CAS  PubMed  Google Scholar 

  44. Burns, F. R. et al. Both rat and mouse T cell receptors specific for the encephalitogenic determinant of myelin basic protein use similar V α and V β chain genes even though the major histocompatibility complex and encephalitogenic determinants being recognized are different. J. Exp. Med. 169, 27–39 (1989).

    Article  CAS  PubMed  Google Scholar 

  45. Heber-Katz, E. & Acha-Orbea, H. The V-region disease hypothesis: evidence from autoimmune encephalomyelitis. Immunol. Today 10, 164–169 (1989).

    Article  CAS  PubMed  Google Scholar 

  46. Sakai, K. et al. Involvement of distinct murine T-cell receptors in the autoimmune encephalitogenic response to nested epitopes of myelin basic protein. Proc. Natl Acad. Sci. USA 85, 8608–8612 (1988).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  47. Behlke, M. A., Chou, H. S., Huppi, K. & Loh, D. Y. Murine T-cell receptor mutants with deletions of βchain variable region genes. Proc. Natl Acad. Sci. USA 83, 767–771 (1986).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  48. Wraith, D. C., Smilek, D. E., Mitchell, D. J., Steinman, L. & McDevitt, H. O. Antigen recognition in autoimmune encephalomyelitis and the potential for peptide-mediated immunotherapy. Cell 59, 247–255 (1989).

    Article  CAS  PubMed  Google Scholar 

  49. Sakai, K. et al. Prevention of experimental encephalomyelitis with peptides that block interaction of T cells with major histocompatibility complex proteins. Proc. Natl Acad. Sci. USA 86, 9470–9474 (1989).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  50. Kappos, L. et al. Induction of a non-encephalitogenic type 2 T helper-cell autoimmune response in multiple sclerosis after administration of an altered peptide ligand in a placebo-controlled, randomized phase II trial. Nature Med. 6, 1176–1182 (2000).

    Article  CAS  PubMed  Google Scholar 

  51. Crowe, P. D., Qin, Y., Conlon, P. J. & Antel, J. P. NBI-5788, an altered MBP83–99 peptide, induces a T-helper 2-like immune response in multiple sclerosis patients. Ann. Neurol. 48, 758–765 (2000).

    Article  CAS  PubMed  Google Scholar 

  52. Lyons, G. A. Letter to shareholders, Neurocrine Biosciences Annual Report [online], (2003).

  53. Sharma, S. D. et al. Antigen-specific therapy of experimental allergic encephalomyelitis by soluble class II major histocompatibility complex-peptide complexes. Proc. Natl Acad. Sci. USA 88, 11465–11469 (1991).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  54. Spack, E. G. Antigen-specific therapies for the treatment of multiple sclerosis: a clinical trial update. Expert Opin. Investig. Drugs 6, 1715–1727 (1997).

    Article  CAS  PubMed  Google Scholar 

  55. Goodkin, D. E. et al. A phase I trial of solubilized DR2:MBP84–102 (AG284) in multiple sclerosis. Neurology 54, 1414–1420 (2000).

    Article  CAS  PubMed  Google Scholar 

  56. Warren, K. G., Catz, I., Ferenczi, L. Z. & Krantz, M. J. Intravenous synthetic peptide MBP8298 delayed disease progression in an HLA Class II-defined cohort of patients with progressive multiple sclerosis: results of a 24-month double-blind placebo-controlled clinical trial and 5 years of follow-up treatment. Eur. J. Neurol. 13, 887–895 (2006).

    Article  CAS  PubMed  Google Scholar 

  57. Bornstein, M. B. et al. A pilot trial of Cop 1 in exacerbating-remitting multiple sclerosis. N. Engl. J. Med. 317, 408–414 (1987).

    Article  CAS  PubMed  Google Scholar 

  58. Johnson, K. P. et al. Copolymer 1 reduces relapse rate and improves disability in relapsing-remitting multiple sclerosis: results of a phase III multicenter, double-blind placebo-controlled trial. The Copolymer 1 Multiple Sclerosis Study Group. Neurology 45, 1268–1276 (1995).

    Article  CAS  PubMed  Google Scholar 

  59. Sela, M., Mozes, E. Therapeutic vaccines in autoimmunity. Proc. Natl Acad. Sci. USA 101 (Suppl. 2), 14586–14592 (2004).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  60. Racke, M. K., Martin, R., McFarland, H. & Fritz, R. B. Copolymer-1-induced inhibition of antigen-specific T cell activation: interference with antigen presentation. J. Neuroimmunol. 37, 75–84 (1992).

    Article  CAS  PubMed  Google Scholar 

  61. Kies, M. W. Panel discussion on species variability and multiple antigens in EAE: summary statement. Ann. NY Acad. Sci. 122, 242–244 (1965).

    Article  CAS  PubMed  Google Scholar 

  62. Steinman, L. The coming of age for antigen-specific therapy of multiple sclerosis. Eur. J. Neurol. 13, 793–794 (2006).

    Article  CAS  PubMed  Google Scholar 

  63. Kuerten S. et al. MBP–PLP fusion protein-induced EAE in C57BL/6 mice. J. Neuroimmunol. 177, 99–111 (2006).

    Article  CAS  PubMed  Google Scholar 

  64. Check, E. Nerve inflammation halts trial for Alzheimer's drug. Nature 415, 462 (2002).

    Article  CAS  PubMed  Google Scholar 

  65. Rogers, J., Strohmeyer, R., Kovelowski, C. J. & Li, R. Microglia and inflammatory mechanisms in the clearance of amyloid β peptide. Glia 40, 260–269 (2002).

    Article  PubMed  Google Scholar 

  66. Esch, T. R., Miskimins, R. & Heber-Katz, E. CAT induces encephalomyelitis in MBP-CAT transgenic mice expressing CAT in oligodendrocytes. Transgene 1, 11–18 (1993).

    Google Scholar 

  67. Hemachudha, T. et al. Myelin basic protein as an encephalitogen in encephalomyelitis and polyneuritis following rabies vaccination. N. Engl. J. Med. 316, 369–374 (1987).

    Article  CAS  PubMed  Google Scholar 

  68. Webster, L. T., & Clow, A. D. Propagation of rabies virus in tissue culture. J. Exp. Med. 66, 125–131 (1937).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  69. Cao, Y. et al. Induction of experimental autoimmune encephalomyelitis in transgenic mice expressing ovalbumin in oligodendrocytes. Eur. J. Immunol. 36, 207–215 (2006).

    Article  CAS  PubMed  Google Scholar 

  70. Smallwood, L. & Baxter, A. G. On lawnmowers and lay-down miseres. Immunology 111, 252–253 (2004).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  71. Levine, S. & Sowinski, R. Experimental allergic encephalomyelitis in inbred and outbred mice. J. Immunol. 110, 139–143 (1973).

    CAS  PubMed  Google Scholar 

  72. Eylar, E. H., Caccam, J., Jackson, J. J., Westall, F. C. & Robinson, A. B. Experimental allergic encephalomyelitis: synthesis of disease-inducing site of the basic protein. Science 168, 1220–1223 (1970).

    Article  CAS  PubMed  Google Scholar 

  73. Shapira, R., Chou, F. C., McKneally, S., Urban, E. & Kibler, R. F. Biological activity and synthesis of an encephalitogenic determinant. Science 173, 736–738 (1971).

    Article  CAS  PubMed  Google Scholar 

  74. Chou, C. H., Chou, F. C., Kowalski, T. J., Shapira, R. & Kibler, R. F. The major site of guinea-pig myelin basic protein encephalitogenic in Lewis rats. J. Neurochem. 28, 115–119 (1977).

    Article  CAS  PubMed  Google Scholar 

  75. Pettinelli, C. B., Fritz, R. B., Chou, C. H. & McFarlin, D. E. Encephalitogenic activity of guinea pig myelin basic protein in the SJL mouse. J. Immunol. 129, 1209–1211 (1982).

    CAS  PubMed  Google Scholar 

  76. Sakai, K. et al. Characterization of a major encephalitogenic T cell epitope in SJL/J mice with synthetic oligopeptides of myelin basic protein. J. Neuroimmunol. 19, 21–32 (1988).

    Article  CAS  PubMed  Google Scholar 

  77. Fritz, R. B., Chou, C. H. & McFarlin, D. E. Relapsing murine experimental allergic encephalomyelitis induced by myelin basic protein. J. Immunol. 130, 1024–1026 (1983).

    CAS  PubMed  Google Scholar 

  78. Lennon, V. A., Wilks, A. V. & Carnegie, P. R. Immunologic properties of the main encephalitogenic peptide from the basic protein of human myelin. J. Immunol. 105, 1223–1230 (1970).

    CAS  PubMed  Google Scholar 

  79. Carnegie, P. R. Amino acid sequence of the encephalitogenic basic protein from human myelin. Biochem. J. 123, 57–67 (1971).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  80. Fujinami, R. S. & Oldstone, M. B. Amino acid homology between the encephalitogenic site of myelin basic protein and virus: mechanism for autoimmunity. Science 230, 1043–1045 (1985).

    Article  CAS  PubMed  Google Scholar 

  81. Goldstein, N. P., Kolb, L. C., Mason, H. L., Sayre, G. P. & Karlson, A. G. Relationship of homologous brain proteolipid to allergic encephalomyelitis in guinea pigs. Neurology 3, 609–614 (1953).

    Article  CAS  PubMed  Google Scholar 

  82. Furlan, R. et al. Vaccination with amyloid-β peptide induces autoimmune encephalomyelitis in C57/BL6 mice. Brain 126, 285–291 (2003).

    Article  PubMed  Google Scholar 

  83. Pellkofer, H. et al. Modelling paraneoplastic CNS disease: T-cells specific for the onconeuronal antigen PNMA1 mediate autoimmune encephalomyelitis in the rat. Brain 127, 1822–1830 (2004).

    Article  PubMed  Google Scholar 

  84. Kojima, K. et al. Experimental autoimmune panencephalitis and uveoretinitis transferred to the Lewis rat by T lymphocytes specific for the S100 beta molecule, a calcium binding protein of astroglia. J. Exp. Med. 180, 817–829 (1994).

    Article  CAS  PubMed  Google Scholar 

  85. Linington, C. et al. T cells specific for the myelin oligodendrocyte glycoprotein mediate an unusual autoimmune inflammatory response in the central nervous system. Eur. J. Immunol. 23, 1364–1372 (1993).

    Article  CAS  PubMed  Google Scholar 

  86. Amor, S. et al. Identification of epitopes of myelin oligodendrocyte glycoprotein for the induction of experimental allergic encephalomyelitis in SJL and Biozzi AB/H mice. J. Immunol. 153, 4349–4356 (1994).

    CAS  PubMed  Google Scholar 

  87. Kaye, J. F. et al. The central nervous system-specific myelin oligodendrocytic basic protein (MOBP) is encephalitogenic and a potential target antigen in multiple sclerosis (MS). J. Neuroimmunol. 102, 189–198 (2000).

    Article  CAS  PubMed  Google Scholar 

  88. Zamvil, S. et al. T-cell clones specific for myelin basic protein induce chronic relapsing paralysis and demyelination. Nature 317, 355–358 (1985).

    Article  CAS  PubMed  Google Scholar 

  89. Kabat, E. A., Wolf, A., Bezer, A. E. Rapid production of acute disseminated encephalomyelitis in rhesus monkeys by injection of brain tissue with adjuvants. Science 104, 362–363 (1946).

    Article  PubMed  Google Scholar 

  90. Lipton, M. M. & Freund, J. The transfer of experimental allergic encephalomyelitis in the rat by means of parabiosis. J. Immunol. 71, 380–384 (1953).

    CAS  PubMed  Google Scholar 

  91. Paterson, P. Y. Transfer of allergic encephalomyelitis in rats by means of lymph node cells. J. Exp. Med. 111, 119–136 (1960).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  92. Waksman, B. H., Arbouys, S. & Arnason, B. G. The use of specific “lymphocyte” antisera to inhibit hypersensitive reactions of the “delayed” type. J. Exp. Med. 114, 997–1022 (1961).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  93. Ben-Nun, A., Wekerle, H. & Cohen, I. R. The rapid isolation of clonable antigen-specific T lymphocyte lines capable of mediating autoimmune encephalomyelitis. Eur. J. Immunol. 11, 195–199 (1981).

    Article  CAS  PubMed  Google Scholar 

  94. Schluesener, H. J., Sobel, R. A., Linington, C. & Weiner, H. L. A monoclonal antibody against a myelin oligodendrocyte glycoprotein induces relapses and demyelination in central nervous system autoimmune disease. J. Immunol. 139, 4016–4021 (1987).

    CAS  PubMed  Google Scholar 

  95. Fierz, W. et al. Synergism in the pathogenesis of EAE induced by an MBP-specific T-cell line and monoclonal antibodies to galactocerebroside or a myelin oligodendroglial glycoprotein. Ann. NY Acad. Sci. 540, 360–363 (1988).

    Article  CAS  PubMed  Google Scholar 

  96. Jiang, H., Zhang, S. I. & Pernis, B. Role of CD8+ T cells in murine experimental allergic encephalomyelitis. Science 256, 1213–1215 (1992).

    Article  CAS  PubMed  Google Scholar 

  97. Koh, D. R. et al. Less mortality but more relapses in experimental allergic encephalomyelitis in CD8−/− mice. Science 256, 1210–1213 (1992).

    Article  CAS  PubMed  Google Scholar 

  98. Genain, C. P. et al. In healthy primates, circulating autoreactive T cells mediate autoimmune disease. J. Clin. Invest. 94, 1339–1345 (1994).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  99. Elliott, J. I., Douek, D. C. & Altmann, D. M. Mice lacking αβ+ T cells are resistant to the induction of experimental autoimmune encephalomyelitis. J. Neuroimmunol. 70, 139–144 (1996).

    Article  CAS  PubMed  Google Scholar 

  100. Nataf, S., Carroll, S. L., Wetsel, R. A., Szalai, A. J. & Barnum, S. R. Attenuation of experimental autoimmune demyelination in complement-deficient mice. J. Immunol. 165, 5867–5873 (2000).

    Article  CAS  PubMed  Google Scholar 

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Acknowledgements

I thank H. Koerner for helpful discussion, M. Jordan for critical review, H. McDevitt for his comments on an early draft of the manuscript and D. Godfrey for his suggestions. This work was funded by the National Health and Medical Research Council of Australia.

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Baxter, A. The origin and application of experimental autoimmune encephalomyelitis. Nat Rev Immunol 7, 904–912 (2007). https://doi.org/10.1038/nri2190

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