CD8+ T cells from Theiler's virus-resistant BALB/cByJ mice downregulate pathogenic virus-specific CD4+ T cells

Lia M. Haynes, Carol L. Vanderlugt, Mauro Carlo Dal Canto, Roger W. Melvold, Stephen D Miller*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

19 Scopus citations

Abstract

Theiler's murine encephalomyelitis virus (TMEV) is a picornavirus which induces an immune-mediated demyelinating disease in susceptible strains of mice and serves as a relevant animal model for multiple sclerosis. Treatment with low dose irradiation prior to infection with the BeAn strain of TMEV renders the genetically resistant BALB/cByJ (C/cByJ) mice susceptible to disease. Previous studies have shown that disease resistance in the C/cByJ is mediated by a 'regulatory' CD8+ T cell population, which does not appear to function via a cytolytic mechanism. We show here that TMEV-specific CD4+ T cell blasts transferred into susceptible, irradiated C/cByJ accelerate clinical disease and enhance TMEV-specific DTH and proliferation in these animals. Significantly, CD8+ cells from infected, resistant C/cByJ mice specifically downregulate the in vivo disease potentiation and diminish virus specific DTH, and proliferative and pro-inflammatory cytokine responses (IFNγ and IL-2) in recipients of TMEV-specific CD4+ T cell blasts. These results indicate that TMEV infection of resistant C/cByJ mice induces a radiosensitive population of regulatory CD8+ T cells which actively downregulate inherent Th1 responses which have disease initiating potential. (C) 2000 Elsevier Science B.V.

Original languageEnglish (US)
Pages (from-to)43-52
Number of pages10
JournalJournal of Neuroimmunology
Volume106
Issue number1-2
DOIs
StatePublished - Jul 1 2000

Keywords

  • EAE/MS
  • Mouse
  • Neuroimmunology
  • T lymphocytes
  • TMEV

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Neurology
  • Clinical Neurology

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