Abrogation of resistance to Theiler's virus-induced demyelination in H- 2b mice deficient in β2-microglobulin

M. Rodriguez, A. J. Dunkel, R. L. Thiemann, J. Leibowitz, M. Zijlstra, R. Jaenisch

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111 Scopus citations

Abstract

Intracerebral infection of susceptible strains of mice with Theiler's virus, a picornavirus, results in central nervous system demyelination, which is similar to multiple sclerosis. Immunogenetic experiments indicate that the MHC (H-2) and, in particular, the D region that controls class I-restricted immune responses, is an important determinant to development of demyelination. We tested whether disruption of β2-microglobulin (β2-m) would abrogate resistance to demyelinating disease normally observed in H- 2b mice. All (C57Bl/6 x 129)F3 mice transgenic for homozygous β2-m gene disruption (-/-) developed chronic demyelination after Theiler's murine encephalomyelitis virus infection, whereas none of the infected littermates with normal expression of class I MHC (β2-m, +/+) developed demyelination. Demyelinated lesions showed class II MHC expression, macrophages, and TNF but no class I MHC expression or CD8+ T cells. No correlation was observed between development of demyelination and delayed-type hypersensitivity responses to virus Ag. Despite the presence of demyelinating lesions, none of the infected β2-m (-/-) mice developed neurologic deficits. Infectious virus and virus Ag persisted in the central nervous systems of infected β2-m (-/- ) mice but not in β2-m (+/+) mice. These experiments support the hypothesis that a class I immune response mediated by CD8+ T cells is important in resistance to Theiler's murine encephalomyelitis virus-induced demyelination. Development of chronic neurologic deficits as observed in immunocompetent susceptible strains of mice may be dependent on the presence of class I MHC and CD8+ T cells.

Original languageEnglish (US)
Pages (from-to)266-276
Number of pages11
JournalJournal of Immunology
Volume151
Issue number1
StatePublished - Jan 1 1993

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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    Rodriguez, M., Dunkel, A. J., Thiemann, R. L., Leibowitz, J., Zijlstra, M., & Jaenisch, R. (1993). Abrogation of resistance to Theiler's virus-induced demyelination in H- 2b mice deficient in β2-microglobulin. Journal of Immunology, 151(1), 266-276.