Adenosine generation catalyzed by CD39 and CD73 expressed on regulatory T cells mediates immune suppression.

Adenosine generation catalyzed by CD39 and CD73 expressed on regulatory T cells mediates immune suppression.
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DOI:
10.1084/jem.20062512
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发表时间:
2007-06-11
期刊:
The Journal of experimental medicine
影响因子:
--
通讯作者:
Robson SC
Robson SC
中科院分区:
其他
文献类型:
--
作者:
Deaglio S;Dwyer KM;Gao W;Friedman D;Usheva A;Erat A;Chen JF;Enjyoji K;Linden J;Oukka M;Kuchroo VK;Strom TB;Robson SC

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T调节细胞(T reg细胞)的研究一直受到缺乏特定表面标记和无法确定抑制机制的限制。我们发现CD39/ENTPD1和CD73/ECTO-5‘-核糖核酸酶的协同表达使CD4+/CD25+/Foxp3+T细胞区别于其他T细胞。这些胞外酶从胞外核苷酸中产生胞外腺苷。CD39/CD73在T细胞上的协同表达和激活的T效应细胞上的腺苷A2A受体产生免疫抑制环,提示在T细胞的抑制功能中起作用。因此,来自CD39缺失小鼠的T-reg细胞在体外表现出受损的抑制特性,并且在体内无法阻止同种异体移植排斥反应。我们得出结论,CD39和CD73是T reg细胞的表面标志,它们传递以腺苷生成为特征的特定生化信号,与细胞免疫调节具有功能相关性。
The study of T regulatory cells (T reg cells) has been limited by the lack of specific surface markers and an inability to define mechanisms of suppression. We show that the expression of CD39/ENTPD1 in concert with CD73/ecto-5′-nucleotidase distinguishes CD4+/CD25+/Foxp3+ T reg cells from other T cells. These ectoenzymes generate pericellular adenosine from extracellular nucleotides. The coordinated expression of CD39/CD73 on T reg cells and the adenosine A2A receptor on activated T effector cells generates immunosuppressive loops, indicating roles in the inhibitory function of T reg cells. Consequently, T reg cells from Cd39-null mice show impaired suppressive properties in vitro and fail to block allograft rejection in vivo. We conclude that CD39 and CD73 are surface markers of T reg cells that impart a specific biochemical signature characterized by adenosine generation that has functional relevance for cellular immunoregulation.
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