The reverse stop-signal model for CTLA4 function

被引:102
作者
Rudd, Christopher E. [1 ,2 ]
机构
[1] Univ Cambridge, Dept Pathol, Div Immunol, Cell Signalling Sect, Cambridge CB1 4QP, England
[2] Cambridge Inst Med Res, Cambridge CB2 OXY, England
基金
英国惠康基金;
关键词
D O I
10.1038/nri2253
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
Activation of the T-cell co-receptor cytotoxic T-lymphocyte antigen 4 (CTLA4) has a pivotal role in adjusting the threshold for T-cell activation and in preventing autoimmunity and massive tissue infiltration by T cells. Although many mechanistic models have been postulated, no single model has yet accounted for its overall function. In this Opinion article, I outline the strengths and weaknesses of the current models, and present a new 'reverse stop-signal model' to account for CTLA4 function.
引用
收藏
页码:153 / 160
页数:8
相关论文
共 86 条
[51]   B7-1 and B7-2 selectively recruit CTLA-4 and CD28 to the immunological synapse [J].
Pentcheva-Hoang, T ;
Egen, JG ;
Wojnoonski, K ;
Allison, JP .
IMMUNITY, 2004, 21 (03) :401-413
[52]   Blockade of CTLA-4 on CD4+ CD25+ regulatory T cells abrogates their function in vivo [J].
Read, Simon ;
Greenwald, Rebecca ;
Izcue, Ana ;
Robinson, Nicholas ;
Mandelbrot, Didier ;
Francisco, Loise ;
Sharpe, Arlene H. ;
Powrie, Fiona .
JOURNAL OF IMMUNOLOGY, 2006, 177 (07) :4376-4383
[53]   The CD28 family: a T-cell rheostat for therapeutic control of T-cell activation [J].
Riley, JL ;
June, CH .
BLOOD, 2005, 105 (01) :13-21
[54]   Unifying concepts in CD28, ICOS and CTLA4 co-receptor signalling [J].
Rudd, CE ;
Schneider, H .
NATURE REVIEWS IMMUNOLOGY, 2003, 3 (07) :544-556
[55]  
RUDD CE, 2002, SCI STKE, pPE18
[56]   Perspective - Emerging challenges in regulatory T cell function and biology [J].
Sakaguchi, Shimon ;
Powrie, Fiona .
SCIENCE, 2007, 317 (5838) :627-629
[57]   CTLA-4 up-regulation of lymphocyte function-associated antigen 1 adhesion and clustering as an alternate basis for coreceptor function [J].
Schneider, H ;
Valk, E ;
Dias, SD ;
Wei, B ;
Rudd, CE .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2005, 102 (36) :12861-12866
[58]   Tyrosine phosphatase SHP-2 binding to CTLA-4: Absence of direct YVKM/YFIP motif recognition [J].
Schneider, H ;
Rudd, CE .
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 2000, 269 (01) :279-283
[59]   Cutting edge:: CTLA-4 (CD152) differentially regulates mitogen-activated protein kinases (extracellular signal-regulated kinase and c-Jun N-terminal kinase) in CD4+ T cells from receptor/ligand-deficient mice [J].
Schneider, H ;
Mandelbrot, DA ;
Greenwald, RJ ;
Ng, F ;
Lechler, R ;
Sharpe, AH ;
Rudd, CE .
JOURNAL OF IMMUNOLOGY, 2002, 169 (07) :3475-3479
[60]  
Schneider H, 1999, J IMMUNOL, V163, P1868