The study identifies T-bet, a novel T box transcription factor, which is specifically expressed in Th1 cells and controls the production of the Th1 cytokine IFNγ. T-bet expression correlates with IFNγ production in Th1, NK, and B cells. Ectopic expression of T-bet in primary T cells induces IFNγ production and represses IL-2 production. Retroviral transduction of T-bet into polarized Th2 cells redirects them into Th1 cells, as evidenced by increased IFNγ production and reduced IL-4 and IL-5 production. T-bet also represses IL-4 and IL-5 production in Th2 cells through an IFNγ-independent pathway. These findings suggest that T-bet initiates Th1 lineage development by activating Th1 genetic programs and repressing Th2 programs. The study highlights the role of T-bet in directing the differentiation of naive T helper cells into distinct Th1 and Th2 lineages.The study identifies T-bet, a novel T box transcription factor, which is specifically expressed in Th1 cells and controls the production of the Th1 cytokine IFNγ. T-bet expression correlates with IFNγ production in Th1, NK, and B cells. Ectopic expression of T-bet in primary T cells induces IFNγ production and represses IL-2 production. Retroviral transduction of T-bet into polarized Th2 cells redirects them into Th1 cells, as evidenced by increased IFNγ production and reduced IL-4 and IL-5 production. T-bet also represses IL-4 and IL-5 production in Th2 cells through an IFNγ-independent pathway. These findings suggest that T-bet initiates Th1 lineage development by activating Th1 genetic programs and repressing Th2 programs. The study highlights the role of T-bet in directing the differentiation of naive T helper cells into distinct Th1 and Th2 lineages.