The Theiler's murine encephalomyelitis virus (TMEV) model for multiple sclerosis shows a strong influence of the murine equivalents of HLA-A, B, and C.
Following intracerebral inoculation of Theiler's murine encephalomyelitis virus (TMEV), susceptible mouse strains develop a chronic demyelinating disease characterized histologically by mononuclear cell-rich infiltrates in the central nervous system (CNS). An immune-mediated basis for this disease is strongly supported by previous studies demonstrating a correlation between clinical disease susceptibility, the presence of particular H-2 region genotypes, and the development of chronically elevated levels of TMEV-specific, MHC class II-restricted delayed-type hypersensitivity (DTH). The present study compared disease susceptibility in (B10.S X SJL)F1 and (B10.S(26R) X SJL)F1 mice which differ only at the D region of the H-2 complex. The data conclusively demonstrates a major influence for homozygosity of H-2s alleles at the H-2D region (the murine equivalent of the human class I HLA-A, B, and C genes) in determining disease susceptibility, as measured by either clinical or histopathological endpoints. In addition, disease susceptibility strongly correlated with the development of high levels of TMEV-specific DTH in the susceptible (B10.S X SJL)F1 strain. However, disease susceptibility did not appear to correlate with TMEV titers in the CNS, TMEV-specific humoral (ELISA and neutralizing) immune responses, or virus-specific splenic T cell proliferative responses. These findings lend additional support to our hypothesis that CNS myelin damage is mediated by a TMEV-specific DTH response. The possible role of class I-restricted responses in the demyelinating process is discussed and murine TMEV-induced demyelinating disease is compared with experimental allergic encephalomyelitis as relevant animal models for human multiple sclerosis.
D000483:Alleles; D000818:Animals; D000914:Antibodies, Viral / Q000032:analysis; D004195:Disease Models, Animal; D004769:Enterovirus Infections / Q000276:immunology*; D006183:H-2 Antigens / Q000235:genetics*; D006968:Hypersensitivity, Delayed / Q000276:immunology; D007113:Immunity, Innate; D008213:Lymphocyte Activation; D008297:Male; D004680:Maus Elberfeld virus / Q000276:immunology; D051379:Mice; D009103:Multiple Sclerosis / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D013116:Spinal Cord / Q000473:pathology*
D000914:Antibodies, Viral; D006183:H-2 Antigens