Class I‐deficient resistant mice intracerebrally inoculated with Theiler's virus show an increased T cell response to viral antigens and susceptibility to demyelination

Lara C. Pullen, Stephen D. Miller, Mauro C. Dal Canto, Byung S. Kim*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

103 Scopus citations

Abstract

Intracerebral inoculation of Theiler's murine encephalomyelitis virus (TMEV) results in immune‐mediated demyelination in susceptible mouse strains. The histology of TMEV‐induced demyelination is similar to that seen in patients suffering from multiple sclerosis. It was previously shown that the susceptibility of mice to TMEV‐induced demyelination in certain strain combinations is closely associated with the major histocompatibility complex (MHC) class I locus. Here we examine disease susceptibility of β2‐microglobulin (β2M)‐deficient transgenic mice lacking class I expression and functional CD8+ T cells. In contrast to TMEV‐infected parental C57BL/6 mice, the transgenics develop high levels of virus‐specific DTH and T cell proliferation accompanied by an increased frequency of central nervous system (CNS) demyelinating lesions. However, clinical signs of demyelination were not noted. Neither antibody titer nor viral persistance were significantly affected in the β2M‐deficient mice. These results suggest that in the absence of functional class I/CD8+ cells, the class II‐restricted T cell response to TMEV is enhanced and CNS pathogenesis is heightened, although the level is not severe enough to result in clinical disease. When the TMEV‐infected mice were subcutaneously immunized with virus, however, the β2M‐deficient mice displayed clinical symptoms. Therefore, our results strongly suggest that CD8+ T cells do not directly contribute to CNS demyelination. In contrast, such T cells appear to be primarily involved in down‐regulation of a potentially damaging CD4+ T cell response in resistant animals, although some of the T cells may play a role in clearing viral persistence in the CNS, resulting in the protection of the host from viral demyelination.

Original languageEnglish (US)
Pages (from-to)2287-2293
Number of pages7
JournalEuropean Journal of Immunology
Volume23
Issue number9
DOIs
StatePublished - Sep 1993

Keywords

  • Class I / Demyelination /Theiler's murine encephalomyelitis virus / β2‐Microglobulin / Susceptibility

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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