Cutting edge: Control of CD8(+) T cell activation by CD4(+)CD25(+) immunoregulatory cells

CD4(+)CD25(+) regulatory T cells inhibit organ-specific autoimmune diseases induced by CD4(+)CD25(-) T cells and are potent suppressors of CD4(+)CD25( -) T cell activation in vitro. We demonstrate that CD4(+)CD25(+) T cells al so suppress both proliferation and IFN-gamma production by CD8(+) T cells i nduced either by polyclonal or Ag-specific stimuli. CD4(+)CD25(+) T cells i nhibit the activation of CD8(+) responders by inhibiting both IL-2 producti on and up-regulation of IL-2R alpha -chain (CD25) expression. Suppression i s mediated via a T-T interaction as activated CD4(+)CD25(+) T cells suppres s the responses of TCR-transgenic CD8(+) T cells stimulated with soluble pe ptide-MHC class I tetramers in the complete absence of APC. These results b roaden the immunoregulatory role played by CD4(+)CD25(+) T cells in the pre vention of autoimmune diseases, but also raise the possibility that they ma y hinder the induction of effector CD8(+) T cells to tumor or foreign Ags.