The TCR ligand-inducible expression of CD73 marks γδ lineage commitment and a metastable intermediate in effector specification
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The TCR ligand-inducible expression of CD73 marks γδ lineage commitment and a metastable intermediate in effector specification. / Coffey, Francis; Lee, Sang-Yun; Buus, Terkild B; Lauritsen, Jens-Peter Holst; Wong, Gladys W; Joachims, Michelle L; Thompson, Linda F; Zúñiga-Pflücker, Juan Carlos; Kappes, Dietmar J; Wiest, David L.
In: The Journal of Experimental Medicine, Vol. 211, No. 2, 10.02.2014, p. 329-43.Research output: Contribution to journal › Journal article › Research › peer-review
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TY - JOUR
T1 - The TCR ligand-inducible expression of CD73 marks γδ lineage commitment and a metastable intermediate in effector specification
AU - Coffey, Francis
AU - Lee, Sang-Yun
AU - Buus, Terkild B
AU - Lauritsen, Jens-Peter Holst
AU - Wong, Gladys W
AU - Joachims, Michelle L
AU - Thompson, Linda F
AU - Zúñiga-Pflücker, Juan Carlos
AU - Kappes, Dietmar J
AU - Wiest, David L
PY - 2014/2/10
Y1 - 2014/2/10
N2 - Numerous studies indicate that γδ T cell receptor (γδTCR) expression alone does not reliably mark commitment of early thymic progenitors to the γδ fate. This raises the possibility that the γδTCR 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 γδ fate. Moreover, we identify CD73 as a TCR ligand-induced cell surface protein that distinguishes γδTCR-expressing CD4(-)CD8(-) progenitors that have committed to the γδ fate from those that have not yet done so. Indeed, unlike CD73(-) γδTCR(+) progenitors, which largely adopt the αβ fate upon separation from the intrathymic selecting environment, those that express CD73 remain CD4(-)CD8(-) and committed to the γδ fate. CD73 is expressed by >90% of peripheral γδ 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 γδ lineage and effector fate are specified sequentially. These findings have important implications for the role of ligand in γδ lineage commitment and its relationship to the specification of effector fate.
AB - Numerous studies indicate that γδ T cell receptor (γδTCR) expression alone does not reliably mark commitment of early thymic progenitors to the γδ fate. This raises the possibility that the γδTCR 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 γδ fate. Moreover, we identify CD73 as a TCR ligand-induced cell surface protein that distinguishes γδTCR-expressing CD4(-)CD8(-) progenitors that have committed to the γδ fate from those that have not yet done so. Indeed, unlike CD73(-) γδTCR(+) progenitors, which largely adopt the αβ fate upon separation from the intrathymic selecting environment, those that express CD73 remain CD4(-)CD8(-) and committed to the γδ fate. CD73 is expressed by >90% of peripheral γδ 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 γδ lineage and effector fate are specified sequentially. These findings have important implications for the role of ligand in γδ lineage commitment and its relationship to the specification of effector fate.
KW - 5'-Nucleotidase
KW - Animals
KW - Cell Lineage
KW - Ligands
KW - Lymphopoiesis
KW - Mice
KW - Mice, Inbred C57BL
KW - Mice, Knockout
KW - Mice, Mutant Strains
KW - Mice, Transgenic
KW - Models, Immunological
KW - Precursor Cells, T-Lymphoid
KW - Receptors, Antigen, T-Cell, gamma-delta
KW - T-Lymphocyte Subsets
KW - Journal Article
KW - Research Support, N.I.H., Extramural
KW - Research Support, Non-U.S. Gov't
U2 - 10.1084/jem.20131540
DO - 10.1084/jem.20131540
M3 - Journal article
C2 - 24493796
VL - 211
SP - 329
EP - 343
JO - The Journal of Experimental Medicine
JF - The Journal of Experimental Medicine
SN - 0022-1007
IS - 2
ER -
ID: 181875905