Regulatory T cells suppress CD8+ T cell responses induced by direct priming and cross-priming and moderate immunodominance disparities

Little is known regarding the participation of CD4(+)CD25(+) regulatory T cells (T-reg) in T-CD8(+) responses. In this study, we show that T-reg depletion via treatment with anti-CD25 mAb (PC61) significantly enhances T-CD8(+) responses to influenza A virus, vaccinia virus, and SV40-transformed cells induced by either direct priming or cross-priming. PC61 did not enhance T-CD8(+) responses in CD4-deficient mice, providing the initial demonstration that PC61 acts on a subset of T-CD4(+), and not on other cells that express either CD25 or a fortuitously cross-reactive Ag. We further show that T-reg selectively suppress responses to the most immunodominant T-CD8(+) determinants in the three systems examined. Therefore, T-reg influence T-CD8 immunodominance hierarchies by moderating disparities in responses to different determinants.