Nature Immunology6, 373 - 381 (2005)
Published online: 6 March 2005; | doi:10.1038/ni1183
The zinc finger protein cKrox directs CD4 lineage differentiation during intrathymic T cell positive selection
Guangping Sun1, Xiaolong Liu1, 4, Peter Mercado1, S Rhiannon Jenkinson1, Magdalini Kypriotou2, Lionel Feigenbaum3, Philippe Galéra2
& Rémy Bosselut1
1
Laboratory of Immune Cell Biology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, USA.
2
Laboratoire de Biochimie du tissu conjonctif, Centre Hospitalier Universitaire de Caen, Faculte de Medecine, Caen, France.
3
Science Applications International Corporation, National Cancer Institute-Frederick Cancer Research and Development Center, Frederick, Maryland 21702, USA.
4
Present address: Shanghai Institute of Biochemistry and Cell Biology, Shanghai, China.
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.
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