The development of T helper (Th) 17 cells requires transforming growth factor (TGF)-β and interleukin (IL)-6 and is independent of the Th1 pathway. Although T cells that produce interferon (IFN)-γ are a recognized feature of Th17 cell responses, mice deficient for STAT4 and T-bet—two prototypical Th1 transcription factors—are protected from autoimmunity associated with Th17 pathogenesis. To examine the fate and pathogenic potential of Th17 cells and origin of IFN-γ-producing T cells that emerge during Th17 immunity, researchers developed IL-17F reporter mice to identify cells committed to expression of IL-17F and IL-17A. Th17 cells require TGF-β for sustained expression of IL-17F and IL-17A. In the absence of TGF-β, both IL-23 and IL-12 acted to suppress IL-17 and enhance IFN-γ production in a STAT4- and T-bet-dependent manner, albeit with distinct efficiencies. These results support a model of late Th17 developmental plasticity with implications for autoimmunity and host defense. Th17 cells are characterized by production of the cytokines interleukin (IL)-17A and IL-17F. Although originally proposed as a branch of the Th1 lineage, IL-17-producing effectors are now thought to develop independently of both Th1 and Th2 lineages. Th17 cells differentiate from naive CD4+ T cell precursors in response to TGF-β and IL-6; the Th1 lineage-associated factors STAT1, T-bet, and STAT4, as well as the Th2 factors STAT6 and GATA3, are dispensable for Th17 differentiation. Th17 development is inhibited by the Th1 cytokine and interferon (IFN)-γ, as well as other cytokines that activate STAT1 (e.g., type I interferons and IL-27), by the Th2 cytokine IL-4. Th17 development is constrained by IL-2 signaling via STAT5. TGF-β, which is required for Th17 development, has suppressive effects on Th1 development through inhibitory effects on STAT4 and T-bet signaling, and also inhibits Th2 development. STAT3 plays a central role in Th17 development, coupling early IL-6 signaling to induction of IL-21, an autocrine factor implicated in the progression of Th17 development. IL-21, also acting in part through STAT3 signaling, can induce expression of the transcription factors RORγt and RORα, which appear to be essential for Th17-lineage specification. Despite the developmental signals that distinguish Th17 and Th1 differentiation, there are interesting parallels between the two developmentalThe development of T helper (Th) 17 cells requires transforming growth factor (TGF)-β and interleukin (IL)-6 and is independent of the Th1 pathway. Although T cells that produce interferon (IFN)-γ are a recognized feature of Th17 cell responses, mice deficient for STAT4 and T-bet—two prototypical Th1 transcription factors—are protected from autoimmunity associated with Th17 pathogenesis. To examine the fate and pathogenic potential of Th17 cells and origin of IFN-γ-producing T cells that emerge during Th17 immunity, researchers developed IL-17F reporter mice to identify cells committed to expression of IL-17F and IL-17A. Th17 cells require TGF-β for sustained expression of IL-17F and IL-17A. In the absence of TGF-β, both IL-23 and IL-12 acted to suppress IL-17 and enhance IFN-γ production in a STAT4- and T-bet-dependent manner, albeit with distinct efficiencies. These results support a model of late Th17 developmental plasticity with implications for autoimmunity and host defense. Th17 cells are characterized by production of the cytokines interleukin (IL)-17A and IL-17F. Although originally proposed as a branch of the Th1 lineage, IL-17-producing effectors are now thought to develop independently of both Th1 and Th2 lineages. Th17 cells differentiate from naive CD4+ T cell precursors in response to TGF-β and IL-6; the Th1 lineage-associated factors STAT1, T-bet, and STAT4, as well as the Th2 factors STAT6 and GATA3, are dispensable for Th17 differentiation. Th17 development is inhibited by the Th1 cytokine and interferon (IFN)-γ, as well as other cytokines that activate STAT1 (e.g., type I interferons and IL-27), by the Th2 cytokine IL-4. Th17 development is constrained by IL-2 signaling via STAT5. TGF-β, which is required for Th17 development, has suppressive effects on Th1 development through inhibitory effects on STAT4 and T-bet signaling, and also inhibits Th2 development. STAT3 plays a central role in Th17 development, coupling early IL-6 signaling to induction of IL-21, an autocrine factor implicated in the progression of Th17 development. IL-21, also acting in part through STAT3 signaling, can induce expression of the transcription factors RORγt and RORα, which appear to be essential for Th17-lineage specification. Despite the developmental signals that distinguish Th17 and Th1 differentiation, there are interesting parallels between the two developmental