A novel transcription factor, T-bet, directs Th1 lineage commitment. T-bet is a Th1-specific T box transcription factor that controls the expression of the hallmark Th1 cytokine, IFNγ. T-bet expression correlates with IFNγ expression in Th1 and NK cells. Ectopic expression of T-bet both transactivates the IFNγ gene and induces endogenous IFNγ production. Remarkably, retroviral gene transduction of T-bet into polarized Th2 and Tc2 primary T cells redirects them into Th1 and Tc1 cells, respectively, as evidenced by the simultaneous induction of IFNγ and repression of IL-4 and IL-5. Thus, T-bet initiates Th1 lineage development from naive Thp cells both by activating Th1 genetic programs and by repressing the opposing Th2 programs. T-bet is a potent transactivator of the IFNγ gene and can simultaneously repress IL-2 gene transcription in stimulated EL4 cells. Retroviral gene transduction of T-bet into primary T cells results in increased IFNγ production. T-bet activates IFNγ and represses IL-4 production in developing Th2 cells. T-bet redirects effector Th2 cells into the Th1 pathway. T-bet represses IL-4 and IL-5 production in Th2 cells through an IFNγ-independent pathway. T-bet redirects effector Tc2 cells into the Tc1 pathway. T-bet converts polarized Th2 cells into Th1 cells relatively little is known about the biological mechanisms through which T box transcription factors exert their functions. T-bet may be involved in cell cycle control and could give a selective growth advantage to infected cells. T-bet converts fully polarized Th2 cells into Th1 cells by a mechanism directly dependent on T-bet expression. T-bet represses IL-4 and IL-5 production in Th2 clones. T-bet clearly regulates IFNγ production in a number of cell types: EL4, primary T cells, developing Th2 cells, effector Th2 and Tc2 cells, and fully polarized Th2 cells. However, in Th2 clones, while T-bet was capable of repressing IL-4 and IL-5 production it was unable to induce substantial IFNγ production. Taken together, these data lead us to conclude that T-bet is responsible for the genetic program that initiates Th1 lineage development from naive Thp cells and acts both by initiating Th1 genetic programs and by repressing the opposing Th2 programs.A novel transcription factor, T-bet, directs Th1 lineage commitment. T-bet is a Th1-specific T box transcription factor that controls the expression of the hallmark Th1 cytokine, IFNγ. T-bet expression correlates with IFNγ expression in Th1 and NK cells. Ectopic expression of T-bet both transactivates the IFNγ gene and induces endogenous IFNγ production. Remarkably, retroviral gene transduction of T-bet into polarized Th2 and Tc2 primary T cells redirects them into Th1 and Tc1 cells, respectively, as evidenced by the simultaneous induction of IFNγ and repression of IL-4 and IL-5. Thus, T-bet initiates Th1 lineage development from naive Thp cells both by activating Th1 genetic programs and by repressing the opposing Th2 programs. T-bet is a potent transactivator of the IFNγ gene and can simultaneously repress IL-2 gene transcription in stimulated EL4 cells. Retroviral gene transduction of T-bet into primary T cells results in increased IFNγ production. T-bet activates IFNγ and represses IL-4 production in developing Th2 cells. T-bet redirects effector Th2 cells into the Th1 pathway. T-bet represses IL-4 and IL-5 production in Th2 cells through an IFNγ-independent pathway. T-bet redirects effector Tc2 cells into the Tc1 pathway. T-bet converts polarized Th2 cells into Th1 cells relatively little is known about the biological mechanisms through which T box transcription factors exert their functions. T-bet may be involved in cell cycle control and could give a selective growth advantage to infected cells. T-bet converts fully polarized Th2 cells into Th1 cells by a mechanism directly dependent on T-bet expression. T-bet represses IL-4 and IL-5 production in Th2 clones. T-bet clearly regulates IFNγ production in a number of cell types: EL4, primary T cells, developing Th2 cells, effector Th2 and Tc2 cells, and fully polarized Th2 cells. However, in Th2 clones, while T-bet was capable of repressing IL-4 and IL-5 production it was unable to induce substantial IFNγ production. Taken together, these data lead us to conclude that T-bet is responsible for the genetic program that initiates Th1 lineage development from naive Thp cells and acts both by initiating Th1 genetic programs and by repressing the opposing Th2 programs.