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TCR‐mediated ThPOK induction promotes development of mature (CD24−) γδ thymocytes
Author(s) -
Park Kyewon,
He Xi,
Lee HyungOk,
Hua Xiang,
Li Yi,
Wiest David,
Kappes Dietmar J
Publication year - 2010
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.1038/emboj.2010.113
Subject(s) - biology , t cell receptor , cd24 , microbiology and biotechnology , immunology , t cell , stem cell , immune system , cancer stem cell
T lymphocytes develop into two major lineages characterized by expression of the αβ and γδ T cell receptor (TCR) heterodimers. Within each major lineage, further specialization occurs, resulting in distinct subsets that differ in TCR specificity, phenotype and functional attributes. Thus, in the murine thymus, two distinct subsets of mature (CD24−) γδ cells have been identified, that is NK1.1+ cells, which are enriched for Vγ1.1 usage and selectively produce IFNγ on stimulation, and CCR6+ cells, which are enriched for Vγ2 usage produce IL17. The upstream signals and transcriptional pathways that promote development of these distinct γδ subsets remain relatively poorly understood. Here, we show that the Zn‐finger transcription factor ThPOK has a critical function in the development of γδ thymocytes. Thus, lack of functional ThPOK causes a marked reduction in the percentage and absolute number of mature γδ thymocytes, and a particularly severe reduction of NK1.1+ cells. Conversely, constitutive ThPOK expression leads to a striking increase in mature NK1.1+ γδ thymocytes. Further, we show that ThPOK induction in γδ thymocytes is induced by strong TCR signals mediated by engagement with antibody or high‐affinity endogenous ligands, and that an important ThPOK cis‐acting element, the distal regulatory element (DRE), is sufficient for this TCR‐dependent induction. These results show that ThPOK expression in γδ thymocytes is regulated in part by the strength of TCR signalling, identify ThPOK as an important mediator of γδ T cell development/maturation, and lend strong support to the view that development of a significant fraction of γδ T cells depends on TCR engagement/signalling.