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

被引:221
作者
Sun, GP
Liu, XL
Mercado, P
Jenkinson, SR
Kypriotou, M
Feigenbaum, L
Galéra, P
Bosselut, R [1 ]
机构
[1] NCI, Lab Immune Cell Biol, Ctr Canc Res, NIH, Bethesda, MD 20892 USA
[2] CHU Caen, Fac Med, Lab Biochim Tissu Conjonctif, F-14000 Caen, France
[3] NCI, Frederick Canc Res & Dev Ctr, Sci Applicat Int Corp, Frederick, MD 21702 USA
关键词
D O I
10.1038/ni1183
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 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.
引用
收藏
页码:373 / 381
页数:9
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