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

Richard J. Clatch, Roger W. Melvold, Mauro C. Dal Canto, Stephen D. Miller, Howard L. Lipton*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

39 Scopus citations

Abstract

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 × SJL)F1 and (B10.S(26R) × 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, diseease susceptibility strongly correlated with the development of high levels of TMEV-specific DTH in the susceptible (B10.S × 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.

Original languageEnglish (US)
Pages (from-to)121-135
Number of pages15
JournalJournal of Neuroimmunology
Volume15
Issue number2
DOIs
StatePublished - Jun 1987

Keywords

  • (Model)
  • HLA-A
  • HLA-B
  • HLA-C
  • Multiple sclerosis
  • Theiler's murine encephalomyelitis virus

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Neurology
  • Clinical Neurology

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