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.
MeSH terms
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Animals
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CD4-Positive T-Lymphocytes / cytology
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CD4-Positive T-Lymphocytes / immunology*
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CD8-Positive T-Lymphocytes / cytology
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CD8-Positive T-Lymphocytes / immunology
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Cell Differentiation / genetics
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Cell Differentiation / immunology*
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Cell Lineage / genetics
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Cell Lineage / immunology
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Humans
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Immunoblotting
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Mice
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Mice, Inbred C57BL
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Mice, Transgenic
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Nerve Tissue Proteins / immunology
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RNA / chemistry
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RNA / genetics
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Receptors, Antigen, T-Cell / immunology
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Repressor Proteins
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Reverse Transcriptase Polymerase Chain Reaction
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T-Lymphocytes, Helper-Inducer / cytology
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T-Lymphocytes, Helper-Inducer / immunology
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Thymus Gland / cytology
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Thymus Gland / immunology
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Transcription Factors / biosynthesis
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Transcription Factors / genetics
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Transcription Factors / immunology*
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Transcription, Genetic / immunology
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Up-Regulation
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Zinc Fingers / genetics
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Zinc Fingers / immunology*
Substances
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Nacc1 protein, mouse
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Nerve Tissue Proteins
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Receptors, Antigen, T-Cell
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Repressor Proteins
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Th-POK protein, mouse
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Transcription Factors
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RNA