V(β)8+ T cells protect from demyelinating disease in a viral model of multiple sclerosis

Kristen M. Drescher, Sean L. Johnston, William Hogancamp, Gerald H. Nabozny, Chella S. David, Ilonna J. Rimm, Peter J. Wettstein, Moses Rodriguez

Research output: Contribution to journalArticle

7 Scopus citations

Abstract

Previous studies illustrated the influence of T cell subsets on susceptibility or resistance to demyelination in the Theiler's murine encephalomyelitis virus (TMEV) model of multiple sclerosis. Genetic segregation analysis showed a correlation with disease phenotype in this model with particular V(β) genes. In this study we investigated the contribution of specific V(β) TCR to the pathogenesis of virus-induced demyelinating disease. Spectratype analysis of cells infiltrating the CNS early in infection demonstrated an over-representation of V(β)8+ T cells in mice expressing a susceptible H-2 haplotype. We infected transgenic mice expressing the V(β)8.2 TCR directed against a non-TMEV antigen and found an increase in demyelinating disease in mice of either susceptible or resistant background compared with littermate controls. In addition, depletion studies with an anti-V(β)8-specific antibody in both susceptible (B10.Q) and resistant (C57BL/6) mice resulted in increased demyelination. TCR analysis of VP2-specific cytotoxic T cell clones from mice with a resistant genotype identified only the V(β)8.1 TCR, suggesting that limited T cell diversity is critical to TMEV clearance. Together, these results support a protective role for V(β)8+ T cells in virus-induced demyelinating disease.

Original languageEnglish (US)
Pages (from-to)271-280
Number of pages10
JournalInternational Immunology
Volume12
Issue number3
DOIs
StatePublished - Jan 1 2000

Keywords

  • Demyelination
  • Theiler's murine encephalomyelitis virus
  • Theiler's virus

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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    Drescher, K. M., Johnston, S. L., Hogancamp, W., Nabozny, G. H., David, C. S., Rimm, I. J., Wettstein, P. J., & Rodriguez, M. (2000). V(β)8+ T cells protect from demyelinating disease in a viral model of multiple sclerosis. International Immunology, 12(3), 271-280. https://doi.org/10.1093/intimm/12.3.271