文章基本信息

标题：Thymic selection can compensate for mutations affecting T cell activation and generate a normal T cell repertoire in mutant mice
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作者：Stephan Kissler ; Linrong Lu ; Harvey Cantor 等
期刊名称：Proceedings of the National Academy of Sciences
印刷版ISSN：0027-8424
电子版ISSN：1091-6490
出版年度：2004
卷号：101
期号：1
页码：210-214
DOI：10.1073/pnas.0307202101
语种：English
出版社：The National Academy of Sciences of the United States of America
摘要：Thymic selection adjusts the reactivity of the peripheral T cell repertoire to maximize recognition of pathogens and minimize stimulation by innocuous substances and self-antigen. The study of molecules implicated in T cell activation often involves the generation of knockout (-/-) mice. In many instances, knockout animals display revealing phenotypes. But should a lack of phenotype be interpreted as a lack of function? Bcl-x{gamma} was shown previously to affect T cell activation in vitro, and here we note that overexpression of this molecule increases cell cycling after T cell receptor ligation by antibody. It was therefore surprising that Bcl-x{gamma}-/-, Bcl-x{gamma} transgenic, and WT T cells displayed similar levels of sensitivity to antigen according to ex vivo stimulation. Bcl-x{gamma} could be demonstrated to influence competitiveness and selection of thymocytes in a manner that counteracted the effects of Bcl-x{gamma} mutation on T cell activation. These findings suggest that thymic selection can overcome genetic defects in T cell activation to generate a T cell repertoire of normal reactivity.
关键词：Bcl-xγ ; TCR ; thymus ; CD5