A critical role for virus-specific CD8+ CTLs in protection from Theiler's virus-induced demyelination in disease-susceptible SJL mice

Meghann Teague Getts, Maureen H. Richards, Stephen D. Miller*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

19 Scopus citations

Abstract

Theiler's murine encephalomyelitis virus (TMEV)-induced demyelinating disease (TMEV-IDD) is a relevant mouse model of multiple sclerosis. Infection of susceptible SJL/J mice leads to life-long CNS virus persistence and development of a chronic T cell-mediated autoimmune demyelinating disease triggered via epitope spreading to endogenous myelin epitopes. Potent CNS-infiltrating CD8+ T cell responses to TMEV epitopes have previously been shown to be induced in both disease-susceptible SJL/J and resistant C57BL/6 mice, in which the virus is rapidly cleared. Specific tolerization of SJL CD8+ T cells specific for the immunodominant TMEV VP3159-166 epitope has no effect on viral load or development of clinical TMEV-IDD, but adoptive transfer of activated CD8+ VP3159-166-specific T cell blasts shortly after TMEV infection to boost the early anti-viral response leads to clearance of CNS virus and protection from subsequent TMEV-IDD. These studies have important implications for vaccine strategies and treatment of chronic infections in humans.

Original languageEnglish (US)
Pages (from-to)102-111
Number of pages10
JournalVirology
Volume402
Issue number1
DOIs
StatePublished - Jun 2010

Keywords

  • Cytotoxic T lymphocytes
  • Disease susceptibility
  • Mutliple sclerosis
  • Theiler's murine encephalomyelitis virus
  • Viral epitopes

ASJC Scopus subject areas

  • Virology

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