Distinct functions for the transcription factors GATA-3 and ThPOK during intrathymic differentiation of CD4(+) T cells

Nat Immunol. 2008 Oct;9(10):1122-30. doi: 10.1038/ni.1647. Epub 2008 Sep 7.


The transcription factors GATA-3 and ThPOK are required for intrathymic differentiation of CD4(+) T cells, but their precise functions in this process remain unclear. Here we show that, contrary to previous findings, Gata3 disruption blocked differentiation into the CD4(+) T cell lineage before commitment to the CD4(+) lineage and in some contexts permitted the 'redirection' of major histocompatibility complex class II-restricted thymocytes into the CD8(+) lineage. GATA-3 promoted ThPOK expression and bound to a region of the locus encoding ThPOK established as being critical for ThPOK expression. Finally, ThPOK promoted differentiation into the CD4(+) lineage in a way dependent on GATA-3 but inhibited differentiation into the CD8(+) lineage independently of GATA-3. We propose that GATA-3 acts as a specification factor for the CD4(+) lineage 'upstream' of the ThPOK-controlled CD4(+) commitment checkpoint.

Publication types

  • Research Support, N.I.H., Intramural

MeSH terms

  • Animals
  • CD4-Positive T-Lymphocytes / cytology*
  • CD4-Positive T-Lymphocytes / immunology
  • CD8-Positive T-Lymphocytes / immunology
  • Cell Differentiation / immunology*
  • Cell Lineage / immunology*
  • Flow Cytometry
  • GATA3 Transcription Factor / immunology*
  • GATA3 Transcription Factor / metabolism
  • Gene Expression Regulation / immunology*
  • Mice
  • Mice, Transgenic
  • Oligonucleotide Array Sequence Analysis
  • Reverse Transcriptase Polymerase Chain Reaction
  • Thymus Gland / cytology
  • Thymus Gland / immunology
  • Transcription Factors / immunology*
  • Transcription Factors / metabolism


  • GATA3 Transcription Factor
  • Gata3 protein, mouse
  • Th-POK protein, mouse
  • Transcription Factors