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.
Original language | English |
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Pages (from-to) | 373-81 |
Number of pages | 9 |
Journal | Nature Immunology |
Volume | 6 |
Issue number | 4 |
DOIs | |
Publication status | Published - Apr 2005 |
Keywords
- Animals
- CD4-Positive T-Lymphocytes
- CD8-Positive T-Lymphocytes
- Cell Differentiation
- Cell Lineage
- Humans
- Immunoblotting
- Mice
- Mice, Inbred C57BL
- Mice, Transgenic
- Nerve Tissue Proteins
- RNA
- Receptors, Antigen, T-Cell
- Repressor Proteins
- Reverse Transcriptase Polymerase Chain Reaction
- T-Lymphocytes, Helper-Inducer
- Thymus Gland
- Transcription Factors
- Transcription, Genetic
- Up-Regulation
- Zinc Fingers