The TCR ligand-inducible expression of CD73 marks γδ lineage commitment and a metastable intermediate in effector specification.
The TCR ligand-inducible expression of CD73 marks γδ lineage commitment and a metastable intermediate in effector specification.
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DOI：
10.1084/jem.20131540
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发表时间：
2014-02-10
期刊：
影响因子：
--
通讯作者：
Wiest DL
中科院分区：
文献类型：
--
作者：
Coffey F;Lee SY;Buus TB;Lauritsen JP;Wong GW;Joachims ML;Thompson LF;Zúñiga-Pflücker JC;Kappes DJ;Wiest DL
CD73的表达是在TCR连接的反应中诱导的，并确定了一群致力于γδ T细胞命运的胸腺细胞。大量研究表明，γδT细胞受体（γδ tcr）的单独表达并不能可靠地标志早期胸腺祖细胞对γδ命运的承诺。这就提出了一种可能性，即γδTCR不能内在地指定命运，而是需要额外的环境因素，包括tcr与配体的结合。我们使用单细胞祖细胞测定来揭示配体有指示性地指导γδ命运的采用。此外，我们发现CD73是一种TCR配体诱导的细胞表面蛋白，它可以区分表达γδTCR的CD4 - CD8 -祖细胞，这些祖细胞已经承诺了γδ的命运，而那些还没有这样做。事实上，与CD73 - γδ tcr +祖细胞不同，CD73 - γδ tcr +祖细胞在脱离胸腺内选择环境后主要采用αβ命运，而那些表达CD73的祖细胞仍然保持CD4 - CD8 -并致力于γδ命运。CD73在90%的外周γδ细胞中表达，表明这在发育过程中是常见的。此外，CD73诱导似乎标志着在获得效应功能之前的亚稳中间阶段，这表明γδ谱系和效应命运是顺序指定的。这些发现对配体在γδ谱系承诺中的作用及其与效应体命运规范的关系具有重要意义。
CD73 expression is induced in response to TCR ligation and identifies a population of thymocytes that are committed to the γδ T cell fate. 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.
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影响因子：
32.4
作者：
Ciofani, Maria;Knowles, Gisele C.;Zuniga-Pflucker, Juan Carlos
通讯作者：
Zuniga-Pflucker, Juan Carlos
影响因子：
32.4
作者：
Chalmin, Fanny;Mignot, Gregoire;Ghiringhelli, Francois
通讯作者：
Ghiringhelli, Francois
影响因子：
4.4
作者：
Lacorazza, HD;Tucek-Szabo, C;Nikolich-Zugich, J
通讯作者：
Nikolich-Zugich, J
DOI：
10.1073/pnas.1010890108
发表时间：
2011-02-22
影响因子：
11.1
作者：
Barbee, Susannah D.;Woodward, Martin J.;Hayday, Adrian C.
通讯作者：
Hayday, Adrian C.
影响因子：
32.4
作者：
Bruno, L;Fehling, HJ;vonBoehmer, H
通讯作者：
vonBoehmer, H