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Critical Reviews™ in Immunology
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ISSN Druckformat: 1040-8401
ISSN Online: 2162-6472

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Critical Reviews™ in Immunology

DOI: 10.1615/CritRevImmunol.v31.i6.10
pages 447-458

Transcription Factor Network Regulating CD+CD8+ Thymocyte Survival

Ruiqing Wang
Division of Immunology, Beckman Research Institute of the City of Hope; Irell & Manella Graduate School of Biological Sciences, City of Hope, Duarte, CA 91010
Huimin Xie
Department of Microbiology & Immunology, College of Medicine, University of Illinois, Chicago, IL
Zhaofeng Huang
Institute of Human Virology, Zhongshan School of Medicine, Sun Yat-Sen University, Guangzhou, 510080 P.R. China
Jian Ma
Division of Immunology, Beckman Research Institute of the City of Hope, Duarte, CA 91010
Xianfeng Fang
Division of Immunology, Beckman Research Institute of the City of Hope, Duarte, CA 91010
Yan Ding
Division of Immunology, Beckman Research Institute of the City of Hope, Duarte, CA 91010
Zuoming Sun
Department of Microbiology & Immunology, College of Medicine, University of Illinois at Chicago; Division of Immunology, Beckman Research Institute of the City of Hope, Duarte, CA 91010

ABSTRAKT

More than 80% of thymocytes are CD4+CD8+ double positive (DP) cells subject to positive/ negative selection. The lifespan of DP thymocytes is critical in shaping the peripheral T-cell repertoire essential for mounting immune responses against foreign, but not self, antigens. During T-cell maturation, if the first round of T-cell receptor (TCR) α chain rearrangement fails to generate a productive T-cell receptor, DP cells start another round of α chain rearrangement until positive selection or cell death intervenes. Thus, the lifespan of DP cells determines how many rounds of α chain rearrangement can be carried out, and influences the likelihood of completing positive selection. The antiapoptotic protein Bcl-xL is the ultimate effector regulating DP cell survival, and several transcription factors critical for T-cell development, such as TCF-1, E proteins, c-Myb, and RORγt, regulate DP survival via a Bcl-xL-dependent pathway. However, the relationship between these transcription factors in this process is largely unclear. Recent results are revealing an interactive network among these critical factors during regulation of DP thymocyte survival. This review will discuss how these transcription factors potentially work together to control DP thymocyte survival that is critical for successful completion of T-cell development.


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