Theiler's murine encephalomyelitis virus (TMEV)-induced demyelinating disease in mice is influenced by the H-2D region: correlation with TEMV-specific delayed-type hypersensitivity.
Intracranial inoculation of Theiler's murine encephalomyelitis virus (TMEV) leads to the development of a chronic demyelinating disorder in certain mouse strains. Development of this disease is controlled by at least two unlinked genes, one of which is within or linked to the H-2 complex. In the present study, we attempted to map the relevant H-2 loci involved in susceptibility to TMEV-induced demyelination using crosses between SJL and several congenic H-2 recombinant mouse strains bearing different combinations of MHC genes from the susceptible H-2s and resistant H-2b haplotypes all on the C57BL/10 strain background. The data suggest that the D region of the H-2 complex strongly influences development of the demyelinating disease because increased susceptibility correlates well with homozygosity for H-2s alleles in the D region, but not in K or I-A. In addition, we also attempted to correlate certain immune and nonimmune pathophysiologic parameters with the development of clinical disease. Specifically, central nervous system TMEV titers and TMEV-specific humoral and cellular [delayed-type hypersensitivity (DTH) and T cell proliferative (Tprlf)] responses were examined. The data show that TMEV-induced demyelinating disease did not correlate with either CNS TMEV titers or TMEV-specific humoral or Tprlf responses but did correlate closely with the presence of high levels of TMEV-specific DTH. Collectively, our findings demonstrating a strong correlation between disease incidence, the presence of particular H-2D region genotypes, and high levels of TMEV-specific DTH in susceptible strains (as well as previous findings showing predominant mononuclear cell infiltrates in CNS demyelinating lesions) support the hypothesis that the disease is immune mediated rather than a result of direct cytolytic effects of virus infection.
D000818:Animals; D000914:Antibodies, Viral / Q000096:biosynthesis; D003711:Demyelinating Diseases / Q000209:etiology / Q000235:genetics* / Q000276:immunology; D004306:Dose-Response Relationship, Immunologic; D004769:Enterovirus Infections / Q000209:etiology / Q000235:genetics* / Q000276:immunology; D005260:Female; D005802:Genes, MHC Class II; D006183:H-2 Antigens / Q000235:genetics*; D064532:Histocompatibility Antigen H-2D; D006968:Hypersensitivity, Delayed / Q000235:genetics* / Q000276:immunology; D007113:Immunity, Innate; D008213:Lymphocyte Activation; D008297:Male; D004680:Maus Elberfeld virus / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D011995:Recombination, Genetic; D013601:T-Lymphocytes / Q000276:immunology; D014779:Virus Replication
D000914:Antibodies, Viral; D006183:H-2 Antigens; D064532:Histocompatibility Antigen H-2D