Basal NF-?B controls IL-7 responsiveness of quiescent naive T cells.

ABSTRACT: T cells are essential for immune defenses against pathogens, such that viability of naïve T cells before antigen encounter is critical to preserve a polyclonal repertoire and prevent immunodeficiencies. The viability of naïve T cells before antigen recognition is ensured by IL-7, which drives expression of the prosurvival factor Bcl-2. Quiescent naïve T cells have low basal activity of the transcription factor NF-?B, which was assumed to have no functional consequences. In contrast to this postulate, our data show that basal nuclear NF-?B activity plays an important role in the transcription of IL-7 receptor ?-subunit (CD127), enabling responsiveness of naïve 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-?B activity is shared by mouse and human naïve T cells. Thus, NF-?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-?B in T cells before antigenic stimulation and identify a novel molecular pathway that controls T-cell homeostasis.

SUBMITTER: Miller ML 

PROVIDER: S-EPMC4034246 | biostudies-literature | 2014 May

REPOSITORIES: biostudies-literature