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

R. J. Clatch, R. W. Melvold, Stephen D Miller, H. L. Lipton

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163 Scopus citations

Abstract

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 demylination using crosses between SJL and several congenic H-2 recombinant mouse strains bearing different combinations of MHC genes from the susceptible H-2(s) and resistant H-2(b) 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-2(s) 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.

Original languageEnglish (US)
Pages (from-to)1408-1414
Number of pages7
JournalJournal of Immunology
Volume135
Issue number2
StatePublished - Dec 1 1985

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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