Repression of the DNA-binding inhibitor Id3 by Blimp-1 limits the formation of memory CD8 + T cells

Yun Ji, Zoltan Pos, Mahadev Rao, Christopher A. Klebanoff, Zhiya Yu, Madhusudhanan Sukumar, Robert N. Reger, Douglas C. Palmer, Zachary A. Borman, Pawel Muranski, Ena Wang, David S. Schrump, Francesco M. Marincola, Nicholas P. Restifo, Luca Gattinoni

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106 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)1230-1237
Number of pages8
JournalNature Immunology
Volume12
Issue number12
DOIs
Publication statusPublished - 12-2011

All Science Journal Classification (ASJC) codes

  • Immunology

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    Ji, Y., Pos, Z., Rao, M., Klebanoff, C. A., Yu, Z., Sukumar, M., Reger, R. N., Palmer, D. C., Borman, Z. A., Muranski, P., Wang, E., Schrump, D. S., Marincola, F. M., Restifo, N. P., & Gattinoni, L. (2011). Repression of the DNA-binding inhibitor Id3 by Blimp-1 limits the formation of memory CD8 + T cells. Nature Immunology, 12(12), 1230-1237. https://doi.org/10.1038/ni.2153