The transcription factor ThPOK is required and sufficient for the generation of CD4+CD8- thymocytes, yet the mechanism by which ThPOK orchestrates differentiation into the CD4+ helper T cell lineage remains unclear. Here we used reporter mice to track the expression of transcription factors in developing thymocytes. Distal promoter-driven expression of the gene encoding the transcription factor Runx3 was restricted to major histocompatibility complex (MHC) class I-selected thymocytes. In ThPOK-deficient mice, such expression was derepressed in MHC class II-selected thymocytes, which contributed to their redirection to the CD8+ T cell lineage. In the absence of both ThPOK and Runx, redirection was prevented and cells potentially belonging to the CD4+ lineage, presumably specified independently of ThPOK, were generated. Our results suggest that MHC class II-selected thymocytes are directed toward the CD4+ lineage independently of ThPOK but require ThPOK to prevent Runx-dependent differentiation toward the CD8+ lineage.

Original languageEnglish
Pages (from-to)1131-1139
Number of pages9
JournalNature immunology
Issue number10
StatePublished - 2008


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