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Repression of the DNA-binding inhibitor Id3 by Blimp-1 limits the formation of memory CD8+ T cells
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Repression of the DNA-binding inhibitor Id3 by Blimp-1 limits the formation of memory CD8+ T cells
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Journal Article
Repression of the DNA-binding inhibitor Id3 by Blimp-1 limits the formation of memory CD8+ T cells
2011
Overview
The molecular basis of CD8
+
memory is still being delineated. Gattinoni
et al
. show that the DNA-binding inhibitor Id3 is critical for the formation of long-lived memory.
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.
Publisher
Nature Publishing Group US,Nature Publishing Group
Subject
/ Animals
/ Basic Helix-Loop-Helix Transcription Factors - deficiency
/ Basic Helix-Loop-Helix Transcription Factors - genetics
/ Biomedical and Life Sciences
/ CD8-Positive T-Lymphocytes - cytology
/ CD8-Positive T-Lymphocytes - immunology
/ CD8-Positive T-Lymphocytes - metabolism
/ Cell Differentiation - genetics
/ DNA
/ Female
/ Genomes
/ Immunologic Memory - immunology
/ Inhibitor of Differentiation Protein 2 - metabolism
/ Inhibitor of Differentiation Proteins - genetics
/ Inhibitor of Differentiation Proteins - metabolism
/ Mice
/ Positive Regulatory Domain I-Binding Factor 1
