c-Rel-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-kappaB family member c-Rel. In resting naive cells c-Rel is associated primarily with IkappaBbeta, an inhibitory molecule that is not effectively degraded by TCR signals. Exposure of T cells to proinflammatory cytokines, TNF-alpha and IL-1beta, shifts c-Rel to IkappaBalpha-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.
Banerjee
Daliya
D
Rosenstiel Research Center and Department of Biology, Brandeis University, Waltham, Massachusetts 02454, USA.
Liou
Hsiou-Chi
HC
Sen
Ranjan
R
D000818:Animals; D017951:Antigen Presentation; D049109:Cell Proliferation; D002478:Cells, Cultured; D016207:Cytokines / Q000235:genetics / Q000378:metabolism* / Q000494:pharmacology; D015870:Gene Expression; D007371:Interferon-gamma / Q000378:metabolism; D007375:Interleukin-1 / Q000378:metabolism; D007376:Interleukin-2 / Q000378:metabolism; D008213:Lymphocyte Activation / Q000187:drug effects / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D008958:Models, Molecular; D020569:Proto-Oncogene Proteins c-rel / Q000502:physiology*; D015398:Signal Transduction / Q000276:immunology; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D016207:Cytokines; D007375:Interleukin-1; D007376:Interleukin-2; D020569:Proto-Oncogene Proteins c-rel; D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma