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Adenosine Generation Catalyzed By CD39 And CD73 Expressed On Regulatory T Cells Mediates Immune Suppression

S. Deaglio, K. Dwyer, Wenda Gao, D. Friedman, A. Usheva, Anna Erat, J. Chen, K. Enjyoji, J. Linden, M. Oukka, V. Kuchroo, T. Strom, S. Robson
Published 2007 · Biology, Medicine

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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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