c-ReI-dependent priming of naive T cells by inflammatory cytokines

The intrinsic refractoriness of naive T cells for cytokine production is counteracted by cells of the innate immune system. Upon sensing danger via Toll-like receptors, these cells upregulate T cell costimulatory molecules and secrete cytokines that enhance T cell activation. We show that cytokine-mediated priming of naive T cells requires the NF-kappa B family member c-Rel. In resting naive cells c-Rel is associated primarily with I kappa B beta, an inhibitory molecule that is not effectively degraded by TCR signals. Exposure of T cells to proinflammatory cytokines, TNF-alpha and IL-1 beta, shifts c-Rel to I kappa B alpha-associated complexes that are readily targeted by the TCR. As a consequence, IL-2 and IFN-gamma mRNA are produced more quickly, and at higher levels, in cytokine-primed T cells. This mechanism does not operate in effector T cells where cytokine gene expression is c-Rel-independent. We propose that c-Rel plays a crucial role as a target of innate signals in T cells.