As shown in Fig. 1 , one of the effects of IL-12 treatment was decreased Foxp3 expression by Tregs. Previous studies showed that IL-2 is required for maximal Foxp3 expression [35] but whether IL-12-mediated reduction in Foxp3 expression occurred through effects on IL-2 signaling was not examined. To address the role for IL-2 signaling in IL-12-mediated effects, we treated cells with exogenous IL-2. IL-2 treatment partially reversed the effect of IL-12, resulting in higher levels of Foxp3 in Tregs (Fig. 9F ). [30] . To determine whether IL-27 has similar effects as IL-12, we treated lymphocyte cultures with anti-CD3 mAb and IL-27 or medium. Similarly to IL-12, IL-27 diminished IL-2 production by Tconvs and CD8 T cells (Fig. 10A ) and down-regulated Foxp3 expression by Tregs (Fig. 10B) . However, unlike IL-12, IL-27 decreased proliferation of Tconvs and Tregs and had no effect on CD8 T cell expansion (Fig. 10C , D) resulting in a relatively slight decrease in Treg frequency (Fig. 10E) . The effects of IL-12 were mediated both by diminished IL-2 expression and changes in the relative amounts of IL-2R on Tregs and Tconvs and CD8 T cells. IL-27 reduced CD25 and CD122 expression on Tregs but only marginally affected expression on non-Tregs (Fig. 10F) . Collectively, these results suggest that Tregs are better able to compete for IL-2 in IL-27 compared to IL-12-treated cultures.