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

Guangping Sun, Xiaolong Liu, Peter Mercado, S Rhiannon Jenkinson, Magdalini Kypriotou, Lionel Feigenbaum, Philippe Galéra, Rémy Bosselut

Research output: Contribution to journalArticle (Academic Journal)peer-review

206 Citations (Scopus)

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 languageEnglish
Pages (from-to)373-81
Number of pages9
JournalNature Immunology
Volume6
Issue number4
DOIs
Publication statusPublished - 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

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