Inhibition of Th1 development mediated by GATA-3 through an IL-4-independent mechanism

Recently, the transcription factor GATA-3 was shown to be selectively expre ssed in Th2 but not Th1 cells and to augment Th2-specific cytokines. Here, we show that loss of GATA-3 expression by developing Th1 cells requires IL- 12 signaling through Stat4 and does not simply result from an absence of IL -4. Moreover, we demonstrate a novel role for GATA-3 in directly repressing Th1 development distinct from its positive actions on Th2-specific cytokin es. GATA-3 inhibits Th1 cytokines by a cell-intrinsic mechanism that is not dependent on IL-4 and that may involve repression of IL-12 signaling. Thus , GATA-3 expression and IL-12 signaling are mutually antagonistic, which fa cilitates rapid dominance of one pathway during early Th development, produ cing a stable divergence in cytokine profiles.