Cutting edge:: CD8+CD122+ regulatory T cells produce IL-10 to suppress IFN-γ production and proliferation of CD8+ T cells

We recently identified CD8(+) CD122(+) regulatory T cells that directly control CD8(+) and CD4(+) cells without intervention of APCs. In this study, we investigated the effector mechanism of CD8+ CD122+ regulatory T cells by using an in vitro regulation system. The profile of cytokine expression revealed that IL-10 was predominantly produced by CD8(+) CD122(+) cells, whereas other cytokines were similarly expressed in CD8+ CD122+ cells and CD8(+) CD122(-) cells. Suppression of both proliferation CD122- cells by and IFN-gamma production by CD8, CD8(+) CD122(+) cells was blocked by adding anti-IL-10 Ab to the culture but not by adding anti-TGF-beta Ab. When IL-10 was removed from the conditioned medium from CD8(+) CD122(+) cells, the conditioned medium no longer showed regulatory activity. Finally, CD8(+) CD122(+) cells from IL-10-deficient mice had no regulatory activity in vitro and reduced regulatory activity in vivo. Our results clearly indicate that IL-10 is produced by CD8(+) CD122(+) cells and mediates the regulatory activity of these cells.