A previous report, using co-cultures of purified Tconvs and Tregs, showed that IL-12 could relieve Treg-mediated suppression of Tconv proliferation and activation [12] . Here, we extend these observations to analyze the effects of IL-12 on T cells in unfractionated lymphoid cultures and identify a basis for at least some of the effects of IL-12. We show that IL-12 decreases IL-2 production by Tconv and CD8 T cells and differentially modulates IL-2R expression on Tregs and non-Tregs. IL-2R is up-regulated on Tconv and CD8 T cells and down-regulated on Tregs. When coupled with decreased IL-2 production, this results in a milieu that favors non-Treg proliferation. The effect of IL-12 on CD25 expression by CD8 T cells is especially notable. In the absence of IL-12, levels of CD25 are much greater on Tregs than CD8 T cells, but treatment with IL-12 at 1 ng/ml results in levels of CD25 on CD8 T cells that exceed those on Tregs in the same culture (Fig. 8B, C) . Levels on CD8 T cells are substantially higher than those on Tconv cells, explaining why IL-12 more readily relieves Treg-mediated suppression of CD8 T cell proliferation. These results are consistent with previous reports showing that IL-2R is down-regulated on Tregs in inflamed tissues in the setting of infectious or autoimmune diseases and that IL-2 levels are reduced at these sites, resulting in the outgrowth of non-Treg T cells [5, 36, 37] .