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

Nat Immunol. 2011 Nov 6;12(12):1230-7. doi: 10.1038/ni.2153.

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.

Publication types

  • Research Support, N.I.H., Intramural

MeSH terms

  • Animals
  • Basic Helix-Loop-Helix Transcription Factors / deficiency
  • Basic Helix-Loop-Helix Transcription Factors / genetics
  • CD8-Positive T-Lymphocytes / cytology
  • CD8-Positive T-Lymphocytes / immunology*
  • CD8-Positive T-Lymphocytes / metabolism
  • Cell Differentiation / genetics
  • Cell Line, Tumor
  • DNA Repair
  • DNA Replication
  • Female
  • Gene Expression Profiling
  • Gene Expression Regulation
  • Immunologic Memory / immunology*
  • Inhibitor of Differentiation Protein 2 / metabolism
  • Inhibitor of Differentiation Proteins / genetics
  • Inhibitor of Differentiation Proteins / metabolism*
  • Lectins, C-Type
  • Mice
  • Mice, 129 Strain
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Positive Regulatory Domain I-Binding Factor 1
  • Promoter Regions, Genetic
  • Receptors, Immunologic / metabolism
  • Transcription Factors / metabolism*

Substances

  • Basic Helix-Loop-Helix Transcription Factors
  • Idb2 protein, mouse
  • Inhibitor of Differentiation Protein 2
  • Inhibitor of Differentiation Proteins
  • Klrg1 protein, mouse
  • Lectins, C-Type
  • Prdm1 protein, mouse
  • Receptors, Immunologic
  • Tcf3 protein, mouse
  • Transcription Factors
  • Idb3 protein, mouse
  • Positive Regulatory Domain I-Binding Factor 1

Associated data

  • GEO/GSE23568