Transcriptional and epigenetic regulation of CD4/CD8 lineage choice

The helper versus cytotoxic-lineage choice of CD4(+)CD8(+) DP thymocytes correlates with MHC restriction of their T cell receptors and the termination of either CD8 or CD4 coreceptor expression. It has been hypothesized that transcription factors regulating the expression of the Cd4/Cd8 coreceptor genes must play a role in regulating the lineage decision of DP thymocytes. Indeed, progress made during the past decade led to the identification of several transcription factors that regulate CD4/CD8 expression that are as well important regulators of helper/cytotoxic cell fate choice. These studies provided insight into the molecular link between the regulation of coreceptor expression and lineage decision. However, studies initiated by the identification of ThPOK, a central transcription factor for helper T cell development, have offered another perspective on the cross-regulation between these two processes. Here, we review advances in our understanding of regulatory circuits composed of transcription factors and their link to epigenetic mechanisms, which play essential roles in specifying and sealing cell lineage identity during the CD4/CD8 commitment process of DP thymocytes.