A ThPOK-LRF transcriptional node maintains the integrity and effector potential of post-thymic CD4(+) T cells

The transcription factor ThPOK promotes CD4(+) T cell differentiation in the thymus. Here, using a mouse strain that allows post-thymic gene deletion, we show that ThPOK maintains CD4(+) T lineage integrity and couples effector differentiation to environmental cues after antigenic stimulation. ThPOK preserved the integrity and amplitude of effector responses, and was required for proper T(H)1 and T(H)2 differentiation in vivo by restraining the expression and function of the transcriptional regulator of cytotoxic T cell differentiation, Runx3. The transcription factor LRF contributed in a redundant manner with ThPOK to prevent the trans-differentiation of mature CD4(+) T cells into CD8(+) T cells. As such, the ThPOK-LRF transcriptional module was essential for CD4(+) T cell integrity and responses.