Abstract
The transcriptional repressor Blimp-1 promotes the differentiation of CD8+ T cells into short-lived effector cells (SLECs) that express the lectin-like receptor KLRG-1, but how it operates remains poorly defined. Here we show that Blimp-1 bound to and repressed the promoter of the gene encoding the DNA-binding inhibitor Id3 in SLECs. Repression of Id3 by Blimp-1 was dispensable for SLEC development but limited the ability of SLECs to persist as memory cells. Enforced expression of Id3 was sufficient to restore SLEC survival and enhanced recall responses. Id3 function was mediated in part through inhibition of the transcriptional activity of E2A and induction of genes regulating genome stability. Our findings identify the Blimp-1–Id3–E2A axis as a key molecular switch that determines whether effector CD8+ T cells are programmed to die or enter the memory pool.
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Acknowledgements
We thank A. Mixon and S. Farid of the Flow Cytometry Unit for help with flow cytometry analyses and sorting, and M. Bachinski for help with editing the manuscript. Supported by the Intramural Research Program of the National Cancer Institute, Center for Cancer Research of the US National Institutes of Health.
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Y.J., Z.P., M.R., C.A.K., Z.Y., M.S., R.N.R., D.C.P., Z.A.B. and L.G. did experiments; Y.J., Z.P., M.R., C.A.K., E.W. and L.G. analyzed experiments; Y.J., Z.P., P.M., D.S.S., F.M.M., N.P.R. and L.G. designed experiments; and Y.J., N.P.R. and L.G. wrote the manuscript.
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Ji, Y., Pos, Z., Rao, M. et al. Repression of the DNA-binding inhibitor Id3 by Blimp-1 limits the formation of memory CD8+ T cells. Nat Immunol 12, 1230–1237 (2011). https://doi.org/10.1038/ni.2153
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DOI: https://doi.org/10.1038/ni.2153
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