V(beta)8(+) T cells protect from demyelinating disease in a viral model ofmultiple sclerosis

Previous studies illustrated the influence of T cell subsets on susceptibil ity or resistance to demyelination in the Theiler's murine encephalomyeliti s virus (TMEV) model of multiple sclerosis. Genetic segregation analysis sh owed a correlation with disease phenotype in this model with particular V-b eta genes. In this study we investigated the contribution of specific V-bet a TCR to the pathogenesis of virus-induced demyelinating disease. Spectraty pe analysis of cells infiltrating the CNS early in infection demonstrated a n over-representation of V(beta)8(+) T cells in mice expressing a susceptib le 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 wit h 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 cytotoxi c T cell clones from mice with a resistant genotype identified only the V(b eta)8.1 TCR, suggesting that limited T cell diversity is critical to TMEV c learance. Together, these results support a protective role for V(beta)8(+) T cells in virus-induced demyelinating disease.