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Coffey F , Lee SY , Buus TB , Lauritsen JP , Wong GW , Joachims ML , Thompson LF , Zuniga-Pflucker JC , Kappes DJ , Wiest DL
The TCR ligand-inducible expression of CD73 marks gammadelta lineage commitment and a metastable intermediate in effector specification
J Exp Med. 2014 Feb 10;211(2) :329-43
PMID: 24493796 PMCID: PMC3920555
AbstractNumerous studies indicate that gammadelta T cell receptor (gammadeltaTCR) expression alone does not reliably mark commitment of early thymic progenitors to the gammadelta fate. This raises the possibility that the gammadeltaTCR is unable to intrinsically specify fate and instead requires additional environmental factors, including TCR-ligand engagement. We use single cell progenitor assays to reveal that ligand acts instructionally to direct adoption of the gammadelta fate. Moreover, we identify CD73 as a TCR ligand-induced cell surface protein that distinguishes gammadeltaTCR-expressing CD4(-)CD8(-) progenitors that have committed to the gammadelta fate from those that have not yet done so. Indeed, unlike CD73(-) gammadeltaTCR(+) progenitors, which largely adopt the alphabeta fate upon separation from the intrathymic selecting environment, those that express CD73 remain CD4(-)CD8(-) and committed to the gammadelta fate. CD73 is expressed by >90% of peripheral gammadelta cells, suggesting this is a common occurrence during development. Moreover, CD73 induction appears to mark a metastable intermediate stage before acquisition of effector function, suggesting that gammadelta lineage and effector fate are specified sequentially. These findings have important implications for the role of ligand in gammadelta lineage commitment and its relationship to the specification of effector fate.
NotesCoffey, Francis Lee, Sang-Yun Buus, Terkild B Lauritsen, Jens-Peter Holst Wong, Gladys W Joachims, Michelle L Thompson, Linda F Zuniga-Pflucker, Juan Carlos Kappes, Dietmar J Wiest, David L United States J Exp Med. 2014 Feb 10;211(2):329-43. doi: 10.1084/jem.20131540. Epub 2014 Feb 3.