T-bet is required for optimal production of IFN-γ and antigen-specific T cell activation by dendritic cells

IFN-gamma is well known as the signature cytokine of CD4(+) T helper 1, CD8(+), and natural killer cells, but recent studies demonstrate that antigen-presenting cells, in particular dendritic cells (DCs), are another potent source for this proinflammatory cytokine. T-bet, a transcription factor that controls IFN-gamma expression in CD4(+) T cells, was reported recently to be expressed in human monocytes and myeloid DCs. In this study we investigate the role of T-bet in this important cell type. The development, differentiation, and activation of bone marrow and splenic IDCs were unimpaired in mice lacking T-bet. However, T-bet was essential for the optimal production of IFN-gamma by both CD8alpha(+) and CD8alpha(-) DCs. T-bet-cleficient IDCs were significantly impaired in their capacity to secrete IFN-gamma after both stimulation with IL-12 alone or in combination with IL-18. Further, T-bet(-/-) DCs were impaired in their ability to activate the T helper 1 program of adoptively transferred antigenspecific T cells in vivo. The rapid up-regulation of T-bet by IFN-gamma in DCs coupled with a function for DC-derived IFN-gamma in T cell activation may constitute a positive feedback loop to maximize type 1 immunity.