In order to delineate the roles of these cytokines, particularly IL-12, on Treg function, we treated lymphocytes harvested from spleens and lymph nodes of naïve mice with a panel of cytokines. Treatment with IL-12 induced IFN-c expression by both Tconv and Tregs and reduced Treg frequency and Foxp3 expression. We also demonstrated that IFN-c + Tregs are as immunosuppressive as IFN-c -Tregs. Our results showed that IL-12 functioned, in part, by diminishing IL-2 production by Tconv and CD8 T cells in the mixed cultures and by down-regulating IL-2 receptor expression on Tregs but up-regulating it on non-Treg T cells.