c-maf is a T helper (Th)2 cell-specific transcription factor, which promotes the differentiation of Th2 cells mainly by an IL-4-dependent mechanism. It remains unclear whether c-maf possesses any IL-4-independent function in regulating the production of Th2 cytokines. Here, we provide evidence demonstrating that c-maf, independent of IL-4, is essential for normal induction of CD25 in developing Th2 cells. The levels of CD25 are significantly higher in developing Th2 cells than in developing Th1 cells during in vitro differentiation. In addition, timely blockade of IL-2 receptor signaling selectively inhibits the production of Th2 cytokines, but not IFN-γ or IL-2. Taken together, our results uncover an IL-4-independent and CD25-mediated function of c-maf in promoting the production of Th2 cytokines.

The local progression of primary tumors is extrinsically controlled by type 1 immune responses, particularly via the cytokine IFN-gamma, whose secretion is highly dependent on helper T cells. The T-box transcription factor T-bet (Tbx21) plays a critical role in the development of type 1 helper T cells and is essential for the production of IFN-gamma. Here, the T-bet pathway in the autochthonous transgenic adenocarcinoma mouse prostate model is demonstrated to have only a modest effect on the characteristics of primary prostate cancers but rather exerts a significant suppressor function in the development of metastatic disease.

The NF-AT family is a group of potent transcription factors that are essential for T cell activation in vitro. However, NF-ATc2-deficient Th cells display hyperproliferation in response to stimulation, suggesting that NF-ATc2 functions as a negative regulator of Th cell activation/proliferation. In this study we show that the transcriptional repressor of GATA (ROG) is a direct target gene of NF-ATc2 and that NF-ATc2-deficient Th cells are unable to fully up-regulate ROG upon stimulation. Restoration of ROG expression in vivo partly corrects the hyperproliferation of NF-ATc2-deficient Th cells by attenuating TCR signals. Our data, therefore, depict a ROG-mediated negative feedback mechanism of T cell activation.