CD8-deficient SJL mice display enhanced susceptibility to Theiler's virus infection and increased demyelinating pathology

W. S. Begolka, L. M. Haynes, J. K. Olson, J. Padilla, K. L. Neville, M. Dal Canto, J. Palma, B. S. Kim, S. D. Miller

Research output: Contribution to journalArticlepeer-review

49 Scopus citations

Abstract

Theiler's murine encephalomyelitis virus (TMEV) infection of the central nervous system (CNS) induces a chronic, progressive demyelinating disease in susceptible mouse strains characterized by inflammatory mononuclear infiltrates and spastic hind limb paralysis. Our lab has previously demonstrated a critical role for TMEV- and myelin-specific CD4+ T cells in initiating and perpetuating this pathology. It has however, also been shown that the MHC class I loci are associated with susceptibility/resistance to TMEV infection and persistence. For this reason, we investigated the contribution of CD8+ T cells to the TMEV-induced demyelinating pathology in the highly susceptible SJL/J mouse strain. Here we show that β2M-deficient SJL mice have similar disease incidence rates to wild-type controls, however β2M-deficient mice demonstrated earlier onset of clinical disease, elevated in vitro responses to TMEV and myelin proteolipid (PLP) epitopes, and significantly higher levels of CNS demyelination and macrophage infiltration at 50 days post-infection. β2M-deficient mice also displayed a significant elevation in persisting viral titers, as well as an increase in macrophage-derived pro-inflammatory cytokine mRNA expression in the spinal cord at this same time point. Taken together, these results indicate that CD8+ T cells are not required for clinical or histologic disease initiation or progression in TMEV-infected SJL mice. Rather, these data stress the critical role of CD4+ T cells in this capacity and further emphasize the potential for CD8+ T cells to contribute to protection from TMEV-induced demyelination.

Original languageEnglish (US)
Pages (from-to)409-420
Number of pages12
JournalJournal of neurovirology
Volume7
Issue number5
DOIs
StatePublished - 2001

Keywords

  • CD8
  • Demyelination
  • Multiple sclerosis
  • Theiler's virus
  • ß2-microglobulin

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