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

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Abstract
The transcription factor ThPOK is required for CD4+ T cell differentiation. Groups led by Taniuchi, Bosselut and Littman define distinct functions for ThPOK and other transcription factors in commitment versus specification of the CD4+ T cell lineage. 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.