The zinc finger protein cKrox directs CD4 lineage differentiation during intrathymic T cell positive selection.
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.
Sun
Guangping
G
Laboratory of Immune Cell Biology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, USA.
Liu
Xiaolong
X
Mercado
Peter
P
Jenkinson
S Rhiannon
SR
Kypriotou
Magdalini
M
Feigenbaum
Lionel
L
Galéra
Philippe
P
Bosselut
Rémy
R
D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology; D002454:Cell Differentiation / Q000235:genetics / Q000276:immunology*; D019070:Cell Lineage / Q000235:genetics / Q000276:immunology; D006801:Humans; D015151:Immunoblotting; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009419:Nerve Tissue Proteins / Q000276:immunology; D012313:RNA / Q000737:chemistry / Q000235:genetics; D011948:Receptors, Antigen, T-Cell / Q000276:immunology; D012097:Repressor Proteins; D020133:Reverse Transcriptase Polymerase Chain Reaction; D006377:T-Lymphocytes, Helper-Inducer / Q000166:cytology / Q000276:immunology; D013950:Thymus Gland / Q000166:cytology / Q000276:immunology; D014157:Transcription Factors / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology*; D014158:Transcription, Genetic / Q000276:immunology; D015854:Up-Regulation; D016335:Zinc Fingers / Q000235:genetics / Q000276:immunology*
D009419:Nerve Tissue Proteins; D012313:RNA; D011948:Receptors, Antigen, T-Cell; D012097:Repressor Proteins; D014157:Transcription Factors; C484605:Nacc1 protein, mouse; C497211:Zbtb7b protein, mouse