Article abstract
Nature Immunology 9, 1122 - 1130 (2008)
Published online: 7 September 2008 | doi:10.1038/ni.1647
Distinct functions for the transcription factors GATA-3 and ThPOK during intrathymic differentiation of CD4+ T cells
Lie Wang1, Kathryn F Wildt1, Jinfang Zhu2, Xianyu Zhang3, Lionel Feigenbaum4, Lino Tessarollo5, William E Paul2, B J Fowlkes3 & Rémy Bosselut1
Abstract
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.
- Laboratory of Immune Cell Biology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, USA.
- Laboratory of Immunology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA.
- Laboratory of Cellular and Molecular Immunology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA.
- National Cancer Institute–Science Applications International Corporation, Frederick, Maryland 21702, USA.
- Mouse Cancer Genetics Program, Center for Cancer Research, National Cancer Institute, Frederick, Maryland 21702, USA.
Correspondence to: Rémy Bosselut1 e-mail: remy@helix.nih.gov
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