Cutting edge: CD8⁺CD122⁺ regulatory T cells produce IL-10 to suppress IFN-γ production and proliferation of CDS⁺ T cells¹

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 and IFN-γ production by CDS CD122^- cells by CD8⁺ CD122⁺ cells was blocked by adding anti-IL-10 Ab to the culture but not by adding anti-TGF-β 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.