Key result
Depletion of Vβ8+ T cells or expression of a non-TMEV Vβ8.2 TCR increased demyelination in mice, supporting a protective role for Vβ8+ T cells in virus-induced demyelinating disease.
Vbeta8+ T cells play a protective role against demyelination in a viral murine model of multiple sclerosis.
Cautions against broad T-cell depletion strategies in demyelination; leaves open translation of Vβ8+ protective effects to human multiple sclerosis.
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(beta) genes. In this study we investigated the contribution of specific V(beta) 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(beta)8(+) T cells in mice expressing a susceptible H-2 haplotype. We infected transgenic mice expressing the V(beta)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(beta)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(beta)8.1 TCR, suggesting that limited T cell diversity is critical to TMEV clearance. Together, these results support a protective role for V(beta)8(+) T cells in virus-induced demyelinating disease.
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Drescher et al. (2000) studied Theiler's murine encephalomyelitis virus (TMEV) model of multiple sclerosis. Vβ8.2 TCR transgenic expression or anti-Vβ8-specific antibody depletion vs. Littermate controls or non-depleted mice was evaluated on Demyelinating disease. Depletion of Vβ8+ T cells or expression of a non-TMEV Vβ8.2 TCR increased demyelination in mice, supporting a protective role for Vβ8+ T cells in virus-induced demyelinating disease.
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