Deletion of the CD4 silencer element supports a stochastic mechanism of thymocyte lineage commitment

被引:66
作者
Leung, RKM
Thomson, K
Gallimore, A
Jones, E
Van den Broek, M
Sierro, S
Alsheikhly, AR
McMichael, A
Rahemtulla, A
机构
[1] Univ Oxford, John Radcliffe Hosp, Nuffield Dept Clin Med, Oxford OX3 9DU, England
[2] Univ Zurich, Inst Pathol, CH-8091 Zurich, Switzerland
[3] Univ Oxford, John Radcliffe Hosp, MRC, Human Immunol Unit, Oxford OX3 9DS, England
基金
英国惠康基金;
关键词
D O I
10.1038/ni733
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 T cell lineage commitment remains controversial; to examine it we deleted the CD4-silencer element in the germ line of a mouse using a combination of gene targeting and Cre/LoxP-mediated recombination. We found that these mice were unable to extinguish CD4 expression either in immature thymocytes or mature CD8(+) cytotoxic T cells (CTLs), which resulted in the development of major histocompatibility complex class II-restricted double-positive CTLs in the periphery. This finding strongly supports a stochastic over an instructive mechanism of coreceptor down-regulation.
引用
收藏
页码:1167 / 1173
页数:7
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