Confusing signals: Recent progress in CTLA-4 biology

被引：288

作者：

Walker, Lucy S. K. ^{[1
]}

Sansom, David M. ^{[1
]}

机构：

[1] UCL, Inst Immun & Transplantat, Div Infect & Immun, London NW3 2PF, England

来源：

TRENDS IN IMMUNOLOGY | 2015年 / 36卷 / 02期

基金：

英国生物技术与生命科学研究理事会; 英国医学研究理事会;

关键词：

CTLA-4; CD28; costimulation; T cell tolerance; T cell activation; REGULATORY T-CELLS; ANTIGEN; 4; CTLA-4; LYMPHOCYTE-ASSOCIATED ANTIGEN-4; MULTIORGAN TISSUE DESTRUCTION; CLATHRIN-ASSOCIATED PROTEIN; TCR STOP-SIGNAL; DENDRITIC CELLS; CUTTING EDGE; COSTIMULATORY MOLECULES; SURFACE EXPRESSION;

D O I：

10.1016/j.it.2014.12.001

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 mechanism of action of cytotoxic T-Iymphocyte-associated protein 4 (CTLA-4) remains surprisingly unclear. Regulatory T (Treg) cells can use CTLA-4 to elicit suppression; however, CTLA-4 also operates in conventional T cells, reputedly by triggering inhibitory signals. Recently, interactions mediated via the CTLA-4 cytoplasmic domain have been shown to preferentially affect Treg cells, yet other evidence suggests that the extracellular domain of CTLA-4 is sufficient to elicit suppression. Here, we discuss these paradoxical findings in the context of CTLA-4-mediated ligand regulation. We propose that the function of CTLA-4 cytoplasmic domain is not to transmit inhibitory signals but to precisely control the turnover, cellular location, and membrane delivery of CTLA-4 to facilitate its central function: regulating the access of CD28 to their shared ligands.

引用

页码：63 / 70

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