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 language | English (US) |
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Pages (from-to) | 271-280 |
Number of pages | 10 |
Journal | International Immunology |
Volume | 12 |
Issue number | 3 |
DOIs | |
State | Published - 2000 |
Keywords
- Demyelination
- Theiler's murine encephalomyelitis virus
- Theiler's virus
ASJC Scopus subject areas
- Immunology and Allergy
- Immunology