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Animal Models of Multiple Sclerosis

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Neural Cell Transplantation

Part of the book series: Methods in Molecular Biology™ ((MIMB,volume 549))

Summary

Since its first description, experimental autoimmune encephalomyelitis, originally designated experimental allergic encephalitis (EAE), has been proposed as animal model to investigate pathogenetic hypotheses and test new treatments in the field of central nervous system inflammation and demyelination, which has become, in the last 30 years, the most popular animal model of multiple sclerosis (MS). This experimental disease can be obtained in all mammals tested so far, including nonhuman primates, allowing very advanced preclinical studies. Its appropriate use has led to the development of the most recent treatments approved for MS, also demonstrating its predictive value when properly handled. Some of the most exciting experiments validating the use of neural precursor cells (NPCs) as a potential therapeutic option in CNS inflammation have been performed in this model. We review here the most relevant immunological features of EAE in the different animal species and strains, and describe detailed protocols to obtain the three most common clinical courses of EAE in mice, with the hope to provide both cultural and practical basis for the use of this fascinating animal model.

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References

  1. Rivers TM, Sprunt DH, Berry GP (1933) Observations on the attempts to produce acutedisseminated encephalomyelitis in monkeys. J Exp Med 58:39–53

    Article  PubMed  CAS  Google Scholar 

  2. Paterson PY (1960) Transfer of allergic encephalomyelitis in rats by means of lymph node cells. J Exp Med 111:119–135

    Article  PubMed  CAS  Google Scholar 

  3. Zamvil SS and Steinman L (1990) The T lymphocyte in experimental allergic encephalomyelitis. Annu Rev Immunol 8:579–621

    Article  PubMed  CAS  Google Scholar 

  4. Schlusener HJ and Wekerle H (1985) Autoaggressive T-lymphocyte lines recognizing the encephalitogenic portion of myelin basic protein: in vitro selection from unprimed rat T-lymphocyte populations. J Immunol 135:3128–3133

    Google Scholar 

  5. Genain CP, Lee-Parritz D, Nguyen MH, Massacesi L, Joshi N, Ferrante R, Hoffman K, Moseley M, Letvin NL, Hauser SL (1994) In healthy primate, circulating autoreactive T cells mediate autoimmune disease. J Clin Invest 4:1339–1345

    Article  PubMed  CAS  Google Scholar 

  6. Ben-Nun A, Wekerle H, Cohen IR (1981) The rapid isolation of clonable antigen specificT lymphocyte linescapable of mediating autoimmune encephalomyelitis. Eur J Immunol 11:195–199

    Article  PubMed  CAS  Google Scholar 

  7. Yamamura T, Namikawa T, Endoh M, Kunishita T, Tabira T (1986) Passive transfer of experimental allergic encephalomyelitis inducedby proteolipid apoprotein. J Neurol Sci 76:269–275

    Article  PubMed  CAS  Google Scholar 

  8. Linington C, Berger T, Perry L, Weerth S, Hinze-Selch D, Zhang Y, Lu HC, Lassmann H, Wekerle H (1993) T cell specific for the myelin oligodendrocyte glycoprotein (MOG) mediate an unusual autoimmune inflammatory response in the central nervous system. Eur J Immunol 23:1364–1372

    Article  PubMed  CAS  Google Scholar 

  9. Linington C, Bradl M, Lassmann H, Brunner C, Vass K (1988) Augmentation of demyelination in rat acute allergic encephalomyelitis by circulating mouse monoclonal antibodies directed against a myelin/oligodendrocyte glycoprotein. Am J Pathol 130:443–454

    PubMed  CAS  Google Scholar 

  10. Massacesi L, Vergelli M, Zehetbauer B, Liuzzi GM, Olivotto J, Ballerini C, Uccelli A, Mancardi GL, Riccio P, Amaducci L (1993) Induction of experimental autoimmune encephalomyelitis in rats and immune response to myelin basic protein in lipid bound form.J Neurol Sci 119:91–98

    Article  PubMed  CAS  Google Scholar 

  11. Kojima K, Berger T, Lassmann H, Hinze-Selch D, Zhang Y, Gehrmann J, Reske K, Wekerle H, Linington C (1994) Experimental autoimmune panencephalitis and uveoretinitis transferred to the Lewis rat by T lymphocytes specific for the S100β molecule, a calcium binding protein of astroglia. J Exp Med 180:817–829

    Article  PubMed  CAS  Google Scholar 

  12. Raine CS (1997) The lesion in multiple sclerosis and chronic relapsing experimental allergic encephalomyelitis: a structural comparison. In Raine CS, McFarland HF, Tourtellotte WW (eds) Multiple sclerosis: clinical and pathogenetic basis. Chapman and Hall, London, pp 242–286

    Google Scholar 

  13. Olitsky PK and Yager RH (1949) Experimental disseminated encephalomyelitis in mice. J Exp Med 90:213–223

    Article  PubMed  CAS  Google Scholar 

  14. Lisak RP, Zweiman B, Kies MW, Driscoll B (1975) Experimental allergic encephalomyelitis in resistant and susceptible guinea pigs: in vivo and in vitro correlates. J Immunol 114:546–549

    PubMed  CAS  Google Scholar 

  15. Brown AM and McFarlin DE (1981) Relapsing experimental allergic encephalomyelitis in the SJL/J mouse. Lab Invest 45:278–284

    PubMed  CAS  Google Scholar 

  16. Mokhtarian F, McFarlin DE, Raine CS (1984) Adoptive transfer of myelin basic proteinsensitized T-cells produces chronic relapsingdemyelinating disease in mice. Nature 309:356–358

    Article  PubMed  CAS  Google Scholar 

  17. Sakai K, Sinha AA, Mitchell DJ, Zamvil SS, Rothbard JB, McDevitt HO (1988) Involvement of distinct murine T-cell receptors in the autoimmune encephalitogenic response to nestedepitopes of myelin basic protein. Proc Natl Acad Sci USA 85:8608–8612

    Article  PubMed  CAS  Google Scholar 

  18. Burns FR, Li RX, Shen L, Offner H, Chou K, Vandenbark A, Haber-Katz E (1989) Both rats and mouse T-cell receptors specific for the encephalitogenic determinant of myelin basic protein use similar Vα and Vβ chain genes even though the major hystocompatibility complex and encephalitogenic determinants being recognized are different. J Exp Med 169:27–39

    Article  PubMed  CAS  Google Scholar 

  19. Lassmann H, Brunner C, Bradl M, Linington C (1988) Experimental allergic encephalomyelitis: the balance between encephalitogenic T lymphocytes and demyelinating antibodies determines size and structure of demyelinated lesions. Acta Neuropathol 75:566–576

    Article  PubMed  CAS  Google Scholar 

  20. Vandenbark AA, Offner H, Reshef T, Fritz RB, Chou C, Cohen IR (1985) Specificity of T lymphocyte lines for peptides of myelin basic protein. J Immunol 139:229–233

    Google Scholar 

  21. Kim G, Tanuma N, Kojima T, Kohyama K, Suzuki Y, Kawazoe Y, Matsumoto Y (1998) CDR3 size spectratyping and sequencing of spectratype-derived TCR of spinal cord T cells in autoimmune encephalomyelitis. J Immunol 160:509–513

    PubMed  CAS  Google Scholar 

  22. Zaller DM, Osman G, Kanagawa O, Hood L (1990) Prevention and treatment of murine experiemental allergic encephalomyelitis with T-cell receptor Vβ specific antibodies. J Exp Med 171:1943–1955

    Article  PubMed  CAS  Google Scholar 

  23. Howell MD, Winters ST, Olee T, Powell HC, Carlo DJ, Brostoff SW (1989) Vaccination against experimental encephalomyelitis with T cell receptor peptides. Science 246:668–670

    Article  PubMed  CAS  Google Scholar 

  24. Lehmann PV, Forsthuber T, Miler A, Sercarz EE (1992) Spreading of T cell autoimmunity to cryptic determinants of an autoantigen. Nature 358:155–157

    Article  PubMed  CAS  Google Scholar 

  25. Offner H, Buenafe AC, Vainiene M, Celnik B, Weinberg AD, Gold DP, Hashim G, Vandenbark AA (1993) Where, when and how to detect biased expression of disease relevant Vβ genes in rats with experimental autoimmune encephalomyelitis. J Immunol 151:506–517

    PubMed  CAS  Google Scholar 

  26. Bauer J, Wekerle H, Lassmann H (1995) Apoptosis in brain-specific autoimmune disease. Curr Opinion Immunol 7:839–843

    Article  CAS  Google Scholar 

  27. Baker D, O’Neill JK, Gschmeissner SE, Wilcox CE, Butter C, Turk JL (1990) Induction of chronic relapsing experimental allergic encephalomyelitis in Biozzi mice. J Nueroimmunol 28:261–270

    Article  CAS  Google Scholar 

  28. Amor S, Groome N, Linington C, Morris MM, Dornmair K, Gardinier MV, Matthieu JM, Baker D (1994) 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

    PubMed  CAS  Google Scholar 

  29. Lorentzen JC, Issazadeh S, Storch M, Mustafa MI, Lassman H, Linington C, Klareskog L, Olsson T (1995) Protracted relapsing and demyelinating experimental autoimmune encephalomyelitis in DA tats immunized with syngeneic spinal cord and incomplete Freund’s adjuvant. J Neuroimmunol 63:193–205

    Article  PubMed  CAS  Google Scholar 

  30. Greer JM, Sobel RA, Sette A, Southwood S, Lees MB, Kuchroo VK (1996) Immunogenic and encephalitogenic epitope clusters of myelin proteolipid protein. J Immunol 156:371–379

    PubMed  CAS  Google Scholar 

  31. Targoni OS, Lehmann PV (1998) Endogenous myelin basic protein inactivates the high avidity T cell repertoire. J Exp Med 187:2055–2063

    Article  PubMed  CAS  Google Scholar 

  32. Sundvall M, Jirholt J, Yang HT, Jansson L, Engstrom A, Pettersson U, Holmdahl R (1995) Identification of murine loci associatedwith susceptibility to chronic experimental autoimmune encephalomyelitis. Nat Genet 10:313–317

    Article  PubMed  CAS  Google Scholar 

  33. Weissert R, Wallstrom E, Storch MK, Stefferl A, Lorentzen J, Lassmann H, Linington C, Olsson T (1998) MHC haplotype-dependent regulation of MOG-induced EAE in rats. J Clin Invest 102:1265–1273

    Article  PubMed  CAS  Google Scholar 

  34. Goverman J Woods A, Larson L Weiner LP, Hood L, Zaller DM (1993) Transgenic mice that express a myelin basic protein-specific T cell receptor develop spontaneous autoimmunity. Cell 72:551–560

    Article  Google Scholar 

  35. Lafaille J, Nagashima K, Katsuki M, Tonegawa S (1994) High incidence of spontaneous autoimmune encephalomyelitis in immunodeficient anti-myelin basic protein T cell receptor transgenic mice. Cell 78:399–408

    Article  PubMed  CAS  Google Scholar 

  36. Kumar V, Sercarz EE (1993) The involvement of T cell receptor peptide-specific regulatory CD4+ T cells in recovery from antigen induced autoimmune disease. J Exp Med 178: 909–916

    Article  PubMed  CAS  Google Scholar 

  37. Jiang H, Zhang SI, Pernis B (1992) Role of CD8+ T cells in murine experimental allergic encephalomyelitis. Science 256:1213–1215

    Article  PubMed  CAS  Google Scholar 

  38. Kozovska MF, Yamamura T, Tabira T (1996) T-T cell interaction between CD4-CD8- regulatory T-cells and T cell clones presenting TCR peptide. Its implications for TCR vaccination against experimental autoimmune encephalomyelitis. J Immunol 157:1781–1790

    PubMed  CAS  Google Scholar 

  39. Huitinga I, Van Rooijen N, De Groot CJA, Uitdehaag BMJ, Dijkstra CD (1990) Suppression of experimental allergic encephalomyelitis in Lewis rats aftre elimination of macrophages. J Exp Med 172:1025–1033

    Article  PubMed  CAS  Google Scholar 

  40. Wolf SD, Dittel BN, Hardardottir F, Janaway CA (1996) Experimental autoimmune encephalomyelitis induction in genetically B-cell deficient mice. J Exp Med 184:2271–2278

    Article  PubMed  CAS  Google Scholar 

  41. Kobayashi Y, Kaway K, Ito K, Honda H, Sobue G, Yoshikai Y (1997) Aggravation of murine experimental allergic encephalomyelitis by administration of T-cell receptor γδ-specific antibodies. J Neuroimmunol 73:169–174

    Article  PubMed  CAS  Google Scholar 

  42. Zhang BN, Yamamura T, Kondo T, Fujiwara M, Tabira T (1997) Regulation of experimental autoimmune encephalomyelitis by natural killer (NK) cells. J Exp Med 186:1677–1687

    Article  PubMed  CAS  Google Scholar 

  43. Naparstek Y, Ben-Nun A, Holoshitz J, Reshef T, Frenkel A, Rosenberg M, Cohen IR (1983) T lymphocyte line producing or vaccinating against autoimmune encephalomyelitis (EAE). Functional activation induces peanut agglutinin receptors and accumulation in the brain and thymus of line cells. Eur J Immunol 13:418–423

    Article  PubMed  CAS  Google Scholar 

  44. Ufret-Vincenty RL, Quigley L, Tresser N, Pak SH, Gado A, Hausmann S, Wucherpfennig KW, Brocke S (1998) In Vivo Survival of Viral Antigen-specific T Cells that Induce Experimental Autoimmune Encephalomyelitis. J Exp Med 1998 188:1725–1738

    Article  CAS  Google Scholar 

  45. Brocke S, Gaur A, Piercy C, Gautam A, Gijbels K, Fathman GC, Steinman L (1993) Induction of relapsing paralysis in experimental autoimmune encephalomyelitis by bacterial superantigen. Nature 365:642–644

    Article  PubMed  CAS  Google Scholar 

  46. Padovan E, Giachino C, Cella M, Valitutti S, Acuto O, Lanzavecchia A (1995) Normal T lymphocytes can express two different T cell receptor β chains: implications for the mechanism of allelic exclusion. J Exp Med 181:1587–1591

    Article  PubMed  CAS  Google Scholar 

  47. Cannella B, Cross AH, Raine CS (1990) Upregulation and coexpression of adhesion molecules correlates with experimental autoimmune demyelination in the central nervous system. J Exp Med 172:1521–1524

    Article  PubMed  CAS  Google Scholar 

  48. Myers KJ, Dougherty JP, Ron Y (1993) In vivo antigen presentation by both brain parenchymal cells and hematopoietically derived cells during the induction of experimental autoimmune encephalomyelitis. J Immunol 15:2252–2260

    Google Scholar 

  49. Traugott U, McFarlin DE, Raine CS (1986) Immunopathology of the lesion in chronic relapsing experimental autoimmune encephalomyelitis in the mouse. Cell Immunol 99:394–410

    Article  Google Scholar 

  50. Olsson T (1994) Role of cytokines in multiple sclerosis and experimental autoimmune encephalomyelitis. Eur J Neurol 1:7–19

    Article  Google Scholar 

  51. Selmaj KW, Raine CS (1988) Tumor necrosis factor mediates myelin and oligodendrocyte damage in vitro. Ann Neurol 23:339–46

    Article  PubMed  CAS  Google Scholar 

  52. Compston DA, Scolding NJ (1991) Immune-mediated oligodendrocyte injury. Ann N Y Acad Sci 633:196–204

    Article  PubMed  CAS  Google Scholar 

  53. Conboy YM, DeKruyff R, Tate KM, Cao ZA, Moore TA, Umetsu DT, Jones PP (1997) Novel genetic regulation of T helper 1 (Th1)/Th2 cytokine production and encephalitogenicity in inbred mouse strains. J Exp Med 185:439–451

    Article  PubMed  CAS  Google Scholar 

  54. Baron JL, Madri JA, Ruddle NH, Hashim G, Janaway CA (1993) Surface expression of α4 integrin by CD4 T cells is required for their entry into brain parenchyma. J Exp Med 177:57–68

    Article  PubMed  CAS  Google Scholar 

  55. Beraud E, Balzano C, Zamora AJ, Varriale S, Bernard D, Ben-Nun A (1993) Pathogenic and non-pathogenic T lymphocytes specific for the encephalitogenic epitope of myelin basic protein: functional characteristics and vaccination properties. J Neuroimmunol 47:41–54

    Article  PubMed  CAS  Google Scholar 

  56. Sun D, Wekerle H (1986) Ia-restricted encephalitogenic T lymphocytes mediating EAE lyse autoantigen-presentig astrocytes. Nature 320:70–72

    Article  PubMed  CAS  Google Scholar 

  57. Jeong MC, Itzikson L, Uccelli A, Brocke S, Oksenberg JR (1998) Differential display analysis of murine encephalitogenic mRNA. Int Immunol 10:1819–1823

    Article  PubMed  CAS  Google Scholar 

  58. Mustafa M, Vingsbo C, Olsson T, Ljungdhal A, Hojeberg B, Holmdahl R (1993) The major histocompatibility complex influences myelin basic protein 68–86-induced T-cell cytokine profile and experimental autoimmune encephalomyelitis. Eur J Immunol 23:3089–3095

    Article  PubMed  CAS  Google Scholar 

  59. Forsthuber T, Yip HC, Lehmann PV (1996) Induction of TH1 and TH2 immunity in neonatal mice. Science 271:1728–1730

    Article  PubMed  CAS  Google Scholar 

  60. Krakowski ML, Owens T (1997) The central nervous system environment controls effector CD4+ T cell cytokine profile in experimental allergic encephalomyelitis. Eur J Immunol 27:2840–2847

    Article  PubMed  CAS  Google Scholar 

  61. Aloisi F, Ria F, Penna G, Adorini L (1998) Microglia are more efficient than astrocytes in antigen processing and in Th1 but not Th2 cell activation. J Immunol 160:4671–4680

    PubMed  CAS  Google Scholar 

  62. Falcone M, Bloom BR (1997) A T helper cell 2 (Th2) immune response against non-self antigens modifies the cytokine profile of autoimmune T cells and protects against experimental allergic encephalomyelitis. J Exp Med 185:901–907

    Article  PubMed  CAS  Google Scholar 

  63. Kuchroo VK, Das MP, Brown JA, Ranger AM, Zamvil SS, Sobel RA, Weiner HL, Nabavi N, Glimcher LH (1995) B7-1 and B7-2 costimulatory molecules activate differentially the Th1/Th2 developmental pathways: application to autoimmune disease therapy. Cell 80:707–718

    Article  PubMed  CAS  Google Scholar 

  64. Nicholson LB, Greer JM, Sobel RA, Lees MB, Kuchroo VK (1995) An altered peptide ligand mediates immune deviation and prevents autoimmune encephalomyelitis. Immunity 3:397–405

    Article  PubMed  CAS  Google Scholar 

  65. Weiner HL (1997) Oral tolerance: immune mechanisms and treatment of autoimmune diseases. Immunol Today 18:335–343

    Article  PubMed  CAS  Google Scholar 

  66. Racke MK, Bonomo A, Scott DE, Cannella B, Levine A, Raine CS, Shevach EM, Rocken M (1994) Cytokine-induced immune deviation as a therapy for inflammatory autoimmune disease. J Exp Med 180:1961–1966

    Article  PubMed  CAS  Google Scholar 

  67. Ruddle NH, Bergman CM, McGrath KM, Lingenheld EG, Grunnet ML, Padula SJ, Clark RB (1990) An antibody to lymphotoxin and tumor necrosis factor prevents transfer of experimental allergic encephalomyelitis. J Exp Med 172:1193–1200

    Article  PubMed  CAS  Google Scholar 

  68. Leonard JP, Waldburger KE, Goldman SJ (1995) Prevention of experimental autoimmune encephalomyelitis by antibodies against interleukin 12. J Exp Med 181:381–386

    Article  PubMed  CAS  Google Scholar 

  69. Genain CP, Abel K, Belmar N, Villinger F, Rosenberg DP, Linington C, Raine CS, Hauser SL (1996) Late complications of immune deviation therapy in a nonhuman primate. Science 274:2054–2057

    Article  PubMed  CAS  Google Scholar 

  70. Taupin V, Renno T, Bourbonniere L, Peterson AC, Rodriguez M, Owens T (1997) Increased severity of experimental autoimmune encephalomyelitis, chronic macrophage/microglial reactivity, and demyelination in transgenic mice producing tumor necrosis factor-alpha in the central nervous system. Eur J Immunol 27:905–913

    Article  PubMed  CAS  Google Scholar 

  71. Frei K, Eugster HP, Bopst M, Constantinescu CS, Lavi E, Fontana A (1997) Tumor necrosis factor alpha and lymphotoxin alpha are not required for induction of acute experimental autoimmune encephalomyelitis. J Exp Med 185:2177–2182

    Article  PubMed  CAS  Google Scholar 

  72. Liu J, Marino MW, Wong G, Grail D, Dunn A, Bettadapura J, Slavin AJ, Old L, Bernard CC (1998) TNF is a potent anti-inflammatory cytokine in autoimmune-mediated demyelination. Nat Med 4:78–83

    Article  PubMed  CAS  Google Scholar 

  73. Ferber IA, Brocke S, Taylor-Edwards C, Ridgway W, Dinisco C, Steinman L, Dalton D, Fathman CG (1996) Mice with a disrupted IFN-gamma gene are susceptible to the induction of experimental autoimmune encephalomyelitis (EAE). J Immunol 156:5–7

    PubMed  CAS  Google Scholar 

  74. Bettelli E, Das MP, Howard ED, Weiner HL, Sobel RA, Kuchroo VK (1998) IL-10 is critical in the regulation of autoimmune encephalomyelitis as demonstrated by studies of IL-10- and IL-4-deficient and transgenic mice. J Immunol 161:3299–3306

    PubMed  CAS  Google Scholar 

  75. Sahrbacher UC, Lechner F, Eugster HP, Frei K, Lassmann H, Fontana A (1998) Mice with an inactivation of the inducible nitric oxide synthase gene are susceptible to experimental autoimmune encephalomyelitis. Eur J Immunol 28:1332–1338

    Article  PubMed  CAS  Google Scholar 

  76. Malipiero U, Frei K, Spanaus KS, Agresti C, Lassmann H, Hahne M, Tschopp J, Eugster HP, Fontana A (1997) Myelin oligodendrocyte glycoprotein-induced autoimmune encephalomyelitis is chronic/relapsing in perforin knockout mice, but monophasic in Fas- and Fas ligand-deficient lpr and gld mice. Eur J Immunol 27:3151–3160

    Article  PubMed  CAS  Google Scholar 

  77. Bontrop RE, Otting N, Slierendregt BL, Lanchbury JS (1995) Evolution of major histocompatibility complex polymorphisms and T-cell receptor diversity in primates. Immunol Rev 143:43–62

    Article  Google Scholar 

  78. Massacesi L, Genain CP, Lee-Parritz D Letvin NL, Canfield D, Hauser SL. (1995) Chronic relapsing experimental autoimmune encephalomyelitis in new world primates. Ann Neurol 37:519–530

    Article  PubMed  CAS  Google Scholar 

  79. Uccelli A, Oksenberg JR, Jeong M, Genain CP, Rombos T, Jaeger E, Lanchbury J, Hauser SL (1997) Characterization of the TCRB chain repertoire in the New World monkey Callithrix jacchus. J Immunol 158:1201–1207

    PubMed  CAS  Google Scholar 

  80. Antunes SG, de Groot NG, Brok H, Doxiadis G, Menezes AA, Otting N, Bontrop RE (1998) The Common Marmoset: a new world primate species with limited MHC class II variability. Proc Natl Acad Sci U S A 95:11745–11750

    Article  PubMed  CAS  Google Scholar 

  81. Genain CP, Nguyen MH, Letvin NL, Pearl R, Davis RL, Adelman L, Lees MB, Linington C, Hauser SL (1995) Antibody facilitation of multiple sclerosis-like lesions in a non-human primate. J Clin Invest 96:2966–2974

    Article  PubMed  CAS  Google Scholar 

  82. Hart BA, Bauer J, Muller HJ, Melchers B, Nicolay K, Brok H, Bontrop RE, Lassmann H, Massacesi L (1998) Histopathological characterization of magnetic resonance imaging-detectable brain white matter lesions in a primate model of multiple sclerosis: a correlative study in the experimental autoimmune encephalomyelitis model in common marmosets (Callithrix jacchus). Am J Pathol 153:649–663

    Article  PubMed  CAS  Google Scholar 

  83. Laman JD, van Meurs M, Schellekens MM, de Boer M, Melchers B, Massacesi L, Lassmann H, Claassen E, ‘t Hart BA (1998) Expression of accessory molecules and cytokines in acute EAE in marmoset monkeys (Callithrix jacchus). J Neuroimmunol 86:30–45

    Article  PubMed  CAS  Google Scholar 

  84. Genain CP, Roberts T, Davis R, Nguyen M, Uccelli A, Faulds D, Hoffman K, Timmel G, Li, Y, Ferrante R, Joshi N, Hedgpeth J, Hauser SL (1995) Prevention of autoimmune demyelination in non-human primates by a cAmp-specific phosphodiesterase inhibitor. Proc Natl Acad Sci USA 92:3601–3605

    Article  PubMed  CAS  Google Scholar 

  85. Shaw CM, Alvord EC, Hruby S (1988) Chronic remitting–relapsing experimental allergic encephalomyelitis induced in monkeys with homologous myelin basic protein. Ann Neurol 24:738–748

    Article  PubMed  CAS  Google Scholar 

  86. Massacesi L, Joshi N, Lee-Parritz D, Rombos A, Letvin NL, Hauser SL (1992) Experimental allergic encephalomyelitis in cynomolgus monkeys. Quantitation of T cell responses in peripheral blood. J Clin Invest 90:399–404

    Article  PubMed  CAS  Google Scholar 

  87. Slierendregt BL, Hall M, ‘t Hart B, Otting N, Anholts J, Verduin W, Claas F, Jonker M, Lanchbury JS, Bontrop RE (1995) Identification of an Mhc-DPB1 allele involved in susceptibility to experimental autoimmune encephalomyelitis in rhesus macaques. Int Immunol 7:1671–1679

    Article  PubMed  CAS  Google Scholar 

  88. Van Lambalgen R, Jonker M (1987) Experimental allergic encephalomyelitis in the rhesus monkey. Treatment of EAE with anti-T lymphocyte subset monoclonal antibodies. Clin Exp Immunol 67:305–312

    Google Scholar 

  89. Meinl E, Hoch RM, Dornmair K de Waal Malefyt R, Bontrop RE, Jonker M, Lassmann H, Hohlfeld R, Wekerle H, ‘t Hart B (1997) Differential encephalitogenic potential of myelin basic protein-specific T cell isolated from normal rhesus macaques. Am J Pathol 150:445–453

    PubMed  CAS  Google Scholar 

  90. Levine S, Sowinski R (1973) Experimental allergic encephalomyelitis in inbred and outbred mice. J Immunol 110:139–43

    PubMed  CAS  Google Scholar 

  91. Theiler M (1934) Spontaneous encephalomyelitis of mice: a new virus disease. Science 80:122

    Article  PubMed  CAS  Google Scholar 

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Furlan, R., Cuomo, C., Martino, G. (2009). Animal Models of Multiple Sclerosis. In: Gordon, D., Scolding, N. (eds) Neural Cell Transplantation. Methods in Molecular Biology™, vol 549. Humana Press, Totowa, NJ. https://doi.org/10.1007/978-1-60327-931-4_11

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