锌指蛋白cKrox在胸腺内T细胞阳性选择过程中指导CD4谱系分化。

The zinc finger protein cKrox directs CD4 lineage differentiation during intrathymic T cell positive selection.

作者信息

Sun Guangping, Liu Xiaolong, Mercado Peter, Jenkinson S Rhiannon, Kypriotou Magdalini, Feigenbaum Lionel, Galéra Philippe, Bosselut Rémy

机构信息

Laboratory of Immune Cell Biology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, USA.

出版信息

Nat Immunol. 2005 Apr;6(4):373-81. doi: 10.1038/ni1183. Epub 2005 Mar 6.

DOI:10.1038/ni1183

PMID:15750595

Abstract

The genetic programs directing CD4 or CD8 T cell differentiation in the thymus remain poorly understood. While analyzing gene expression during intrathymic T cell selection, we found that Zfp67, encoding the zinc finger transcription factor cKrox, was upregulated during the differentiation of CD4(+) but not CD8(+) T cells. Expression of a cKrox transgene impaired CD8 T cell development and caused major histocompatibility complex class I-restricted thymocytes to differentiate into CD4(+) T cells with helper properties rather than into cytotoxic CD8(+) T cells, as normally found. CD4 lineage differentiation mediated by cKrox required its N-terminal BTB (bric-a-brac, tramtrack, broad complex) domain. These findings identify cKrox as a chief CD4 differentiation factor during positive selection.

摘要

指导胸腺中CD4或CD8 T细胞分化的基因程序仍知之甚少。在分析胸腺内T细胞选择过程中的基因表达时，我们发现编码锌指转录因子cKrox的Zfp67在CD4(+)而非CD8(+) T细胞分化过程中上调。cKrox转基因的表达损害了CD8 T细胞的发育，并使主要组织相容性复合体I类限制性胸腺细胞分化为具有辅助特性的CD4(+) T细胞，而非正常情况下的细胞毒性CD8(+) T细胞。由cKrox介导的CD4谱系分化需要其N端的BTB（bric-a-brac、tramtrack、broad complex）结构域。这些发现确定cKrox是阳性选择过程中的主要CD4分化因子。