Low constitutive expression of the transcription factor GATA-3 in naive T cells and the fact that dendritic cells do not produce interleukin 4 (IL-4) are consistent with the idea of a default T helper type 2 (TH2) program for CD4+ T cells. In Immunity, Zhou et al. show that many redundant pathways induce expression of the TH1 transcription factor T-bet, but in the absence of T-bet, activated T cells default into an endogenous TH2 program characterized by GATA-3 upregulation and IL-4 production by T cells. IL-12 and interferon-γ are redundant for the induction of T-bet expression in cells responding to signaling via the T cell antigen receptor (TCR). In the absence of T-bet, which inhibits the expression of GATA-3 and IL-4, GATA-3 drives TH2 differentiation even in the absence of IL-4. Stimuli other than IL-12 and interferon-γ can also induce T-bet in vivo; type I interferon or IL-27 represent possible candidates.

Immunity 37, 660–673 (2012)