Basal NF-κB controls IL-7 responsiveness of quiescent naive T cells

T cells are essential for immune defenses against pathogens, such that viability of naive T cells before antigen encounter is critical to preserve a polyclonal repertoire and prevent immunodeficiencies. The viability of naive T cells before antigen recognition is ensured by IL-7, which drives expression of the prosurvival factor Bcl-2. Quiescent naive T cells have low basal activity of the transcription factor NF-kappa B, which was assumed to have no functional consequences. In contrast to this postulate, our data show that basal nuclear NF-kappa B activity plays an important role in the transcription of IL-7 receptor alpha-subunit (CD127), enabling responsiveness of naive T cells to the prosurvival effects of IL-7 and allowing T-cell persistence in vivo. Moreover, we show that this property of basal NF-kappa B activity is shared by mouse and human naive T cells. Thus, NF-kappa B drives a distinct transcriptional program in T cells before antigen encounter by controlling susceptibility to IL-7. Our results reveal an evolutionarily conserved role of NF-kappa B in T cells before antigenic stimulation and identify a novel molecular pathway that controls T-cell homeostasis.