Abstract
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-κB family member c-Rel. In resting naive cells c-Rel is associated primarily with IκBβ, an inhibitory molecule that is not effectively degraded by TCR signals. Exposure of T cells to proinflammatory cytokines, TNF-α and IL-1β, shifts c-Rel to IκBα-associated complexes that are readily targeted by the TCR. As a consequence, IL-2 and IFN-γ 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.
Original language | English (US) |
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Pages (from-to) | 445-458 |
Number of pages | 14 |
Journal | Immunity |
Volume | 23 |
Issue number | 4 |
DOIs | |
State | Published - Oct 2005 |
Externally published | Yes |
ASJC Scopus subject areas
- Immunology and Allergy
- Infectious Diseases
- Immunology