Distinct functions for the transcription factors GATA-3 and ThPOK during intrathymic differentiation of CD4+ T cells
Nature immunology, 2008•nature.com
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 …
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 …
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.
nature.com