Treg development, homeostasis and suppressive function are dependent upon IL-2 [25] [26] [27] [28] [29] . Further, IL-12 diminishes IL-2 expression by CD4 T cells [30] . Initially, we showed that IL-2 expression by Tconvs was modestly reduced after 48 hr with more substantial effects noted after 72 hr of IL-12 treatment (Fig. 8A ). More strikingly, IL-2 production by CD8 T cells was greatly reduced after both 48 and 72 hr (Fig. 8A ). In agreement with this diminished expression, levels of IL-2, measured by ELISA, were reduced in IL-12-treated cultures at 48 hr (Fig. 8B) . T cell proliferation is augmented by IL-2, especially in tissues at sites of inflammation [31] [32] [33] , yet the results in Fig. 1 show that Tconv proliferation is increased by IL-12 treatment. One possible explanation for these results is that IL-12 preferentially induces Effects of IL-12 on IL-2 and IL-2R Expression PLOS ONE | www.plosone.org IL-2R expression on Tconvs; IL-12 was previously shown to enhance IL-2R expression on CD8 T cells [34] . As shown in Fig. 9 (A-B, D-E), this is indeed the case. Treatment with IL-12 in the presence of anti-CD3 mAb induced up-regulation of both the a (CD25) and b (CD122) chains of the IL-2R on Tconv and CD8 T cells in a dose-dependent manner. In contrast, IL-12 treatment diminished CD25 expression on Tregs while not affecting CD122 expression, reducing the ability of Tregs to compete for IL-2 in the culture. Of note, even though IL-12 induced increased IFN-c expression by Tconv and CD8 T cells, IFN-c, by itself, was unable to induce diminished expression of IL-2 (Fig. 8B) or IL-2R upregulation on non-Treg T cells (Fig. 9C) .