Transcriptional control of rapid recall by memory CD4 T cells.

ABSTRACT: Memory T cells are distinguished from naive T cells by their rapid production of effector cytokines, although mechanisms for this recall response remain undefined. In this study, we investigated transcriptional mechanisms for rapid IFN-? production by Ag-specific memory CD4 T cells. In naive CD4 T cells, IFN-? production only occurred after sustained Ag activation and was associated with high expression of the T-bet transcription factor required for Th1 differentiation and with T-bet binding to the IFN-? promoter as assessed by chromatin immunoprecipitation analysis. By contrast, immediate IFN-? production by Ag-stimulated memory CD4 T cells occurred in the absence of significant nuclear T-bet expression or T-bet engagement on the IFN-? promoter. We identified rapid induction of NF-?B transcriptional activity and increased engagement of NF-?B on the IFN-? promoter at rapid times after TCR stimulation of memory compared with naive CD4 T cells. Moreover, pharmacologic inhibition of NF-?B activity or peptide-mediated inhibition of NF-?B p50 translocation abrogated early memory T cell signaling and TCR-mediated effector function. Our results reveal a molecular mechanism for memory T cell recall through enhanced NF-?B p50 activation and promoter engagement, with important implications for memory T cell modulation in vaccines, autoimmunity, and transplantation.

SUBMITTER: Lai W 

PROVIDER: S-EPMC3131107 | biostudies-literature | 2011 Jul

REPOSITORIES: biostudies-literature