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

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.