| First Author | Lai W | Year | 2011 |
| Journal | J Immunol | Volume | 187 |
| Issue | 1 | Pages | 133-40 |
| PubMed ID | 21642544 | Mgi Jnum | J:176184 |
| Mgi Id | MGI:5288586 | Doi | 10.4049/jimmunol.1002742 |
| Citation | Lai W, et al. (2011) Transcriptional control of rapid recall by memory CD4 T cells. J Immunol 187(1):133-40 |
| abstractText | 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-gamma production by Ag-specific memory CD4 T cells. In naive CD4 T cells, IFN-gamma 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-gamma promoter as assessed by chromatin immunoprecipitation analysis. By contrast, immediate IFN-gamma 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-gamma promoter. We identified rapid induction of NF-kappaB transcriptional activity and increased engagement of NF-kappaB on the IFN-gamma promoter at rapid times after TCR stimulation of memory compared with naive CD4 T cells. Moreover, pharmacologic inhibition of NF-kappaB activity or peptide-mediated inhibition of NF-kappaB 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-kappaB p50 activation and promoter engagement, with important implications for memory T cell modulation in vaccines, autoimmunity, and transplantation. |
