Repression of the transcription factor Th-POK by Runx complexes in cytotoxic T cell development

Mouse CD4(+) CD8(+) double- positive ( DP) thymocytes differentiate into CD4(+) helper- lineage cells upon expression of the transcription factor Th- POK but commit to the CD8(+) cytotoxic lineage in its absence. We report the redirected differentiation of class I - restricted thymocytes into CD4(+) CD8(-) helper- like T cells upon loss of Runx transcription factor complexes. A Runx- binding sequence within the Th- POK locus acts as a transcriptional silencer that is essential for Th- POK repression and for development of CD8(+) T cells. Thus, Th- POK expression and genetic programming for T helper cell development are actively inhibited by Runx- dependent silencer activity, allowing for cytotoxic T cell differentiation. Identification of the transcription factors network in CD4 and CD8 lineage choice provides insight into how distinct T cell subsets are developed for regulating the adaptive immune system.