Kreslavsky Taras, Savage Adam K, Hobbs Robin, Gounari Fotini, Bronson Roderick, Pereira Pablo, Pandolfi Pier Paolo, Bendelac Albert, von Boehmer Harald
Laboratory of Lymphocyte Biology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA.
Proc Natl Acad Sci U S A. 2009 Jul 28;106(30):12453-8. doi: 10.1073/pnas.0903895106. Epub 2009 Jul 15.
Some gammadelta and alphabeta T lymphocytes exhibit an "innate" phenotype associated with rapid cytokine responses. The PLZF transcription factor is essential for the innate phenotype of NKT cells. This report shows that PLZF is likewise responsible for the innate, NKT-like phenotype of Vgamma1+Vdelta6.3/Vdelta6.4+ cells. TCR cross-linking induced PLZF expression in all polyclonal immature gammadelta thymocytes, suggesting that agonist selection might be required for PLZF induction. Transgenic expression of Vgamma1Vdelta6.4 TCR was sufficient to support the development of large numbers of PLZF+ T cells, further supporting the importance of the TCR for PLZF induction. Interestingly, expression of this TCR transgene led to the development of spontaneous dermatitis.
一些γδ和αβ T淋巴细胞表现出与快速细胞因子反应相关的“固有”表型。PLZF转录因子对NKT细胞的固有表型至关重要。本报告表明,PLZF同样负责Vγ1+Vδ6.3/Vδ6.4+细胞的固有、NKT样表型。TCR交联在所有多克隆未成熟γδ胸腺细胞中诱导PLZF表达,这表明PLZF诱导可能需要激动剂选择。Vγ1Vδ6.4 TCR的转基因表达足以支持大量PLZF+ T细胞的发育,进一步支持了TCR对PLZF诱导的重要性。有趣的是,这种TCR转基因的表达导致了自发性皮炎的发生。