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.