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

被引:159
作者
Ji, Yun [1 ]
Pos, Zoltan [2 ,3 ]
Rao, Mahadev [1 ]
Klebanoff, Christopher A. [1 ]
Yu, Zhiya [1 ]
Sukumar, Madhusudhanan [1 ]
Reger, Robert N. [1 ]
Palmer, Douglas C. [1 ]
Borman, Zachary A. [1 ]
Muranski, Pawel [1 ]
Wang, Ena [2 ,3 ]
Schrump, David S. [1 ]
Marincola, Francesco M. [2 ,3 ]
Restifo, Nicholas P. [1 ]
Gattinoni, Luca [1 ]
机构
[1] NCI, US Natl Inst Hlth, Ctr Canc Res, Bethesda, MD 20892 USA
[2] US Natl Inst Hlth, Dept Transfus Med, Ctr Clin, Infect Dis & Immunogenet Sect, Bethesda, MD USA
[3] US Natl Inst Hlth, Ctr Human Immunol, Bethesda, MD USA
基金
美国国家卫生研究院;
关键词
EFFECTOR; DIFFERENTIATION; EXPRESSION; CANCER; E2A; PROLIFERATION; AMPLIFICATION; LYMPHOCYTES; MAINTENANCE; MATURATION;
D O I
10.1038/ni.2153
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
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.
引用
收藏
页码:1230 / U126
页数:9
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