VACCINATION WITH BV8S2 PROTEIN AMPLIFIES TCR-SPECIFIC REGULATION AND PROTECTION AGAINST EXPERIMENTAL AUTOIMMUNE ENCEPHALOMYELITIS IN TCR BV8S2 TRANSGENIC MICE

TCR determinants overexpressed by autopathogenic Th1 cells can natural ly induce a second set of TCR-specific regulatory T cells. We addresse d the question of whether immune regulation could be induced naturally in a genetically restricted model in which a major portion of TCR-spe cific regulatory T cells expressed the same target TCR BV8S2 chain as the pathogenic T cells specific for myelin basic protein (MBP), We fou nd vigorous T cell responses to BV8S2 determinants in naive mice that could be further potentiated by vaccination with heterologous BV8S2 pr oteins, resulting in the selective inhibition of MBP-specific Th1 cell s and protection against experimental encephalomyelitis. Moreover, coc ulture with BV8S2-specific T cells or their supernatants reduced proli feration, IFN-gamma secretion, and encephalitogenic activity of MBP-sp ecific T cells, These results suggest that immune regulation occurs th rough a nondeletional cytokine-driven suppressive mechanism.