Transcriptional Control of Rapid Recall by Memory CD4 T Cells

  • Lai W
  • Yu M
  • Huang M
  • et al.
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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-γ production by Ag-specific memory CD4 T cells. In naive CD4 T cells, IFN-γ 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-γ promoter as assessed by chromatin immunoprecipitation analysis. By contrast, immediate IFN-γ 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-γ promoter. We identified rapid induction of NF-κB transcriptional activity and increased engagement of NF-κB on the IFN-γ promoter at rapid times after TCR stimulation of memory compared with naive CD4 T cells. Moreover, pharmacologic inhibition of NF-κB activity or peptide-mediated inhibition of NF-κB 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-κB p50 activation and promoter engagement, with important implications for memory T cell modulation in vaccines, autoimmunity, and transplantation.

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APA

Lai, W., Yu, M., Huang, M.-N., Okoye, F., Keegan, A. D., & Farber, D. L. (2011). Transcriptional Control of Rapid Recall by Memory CD4 T Cells. The Journal of Immunology, 187(1), 133–140. https://doi.org/10.4049/jimmunol.1002742

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