Adenosine generation catalyzed by CD39 and CD73 expressed on regulatory T cells mediates immune suppression |
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| Authors: | Deaglio Silvia Dwyer Karen M Gao Wenda Friedman David Usheva Anny Erat Anna Chen Jiang-Fan Enjyoji Keiichii Linden Joel Oukka Mohamed Kuchroo Vijay K Strom Terry B Robson Simon C |
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| Affiliation: | Department of Medicine, Harvard Medical School, Transplantation Research Center, Beth Israel Deaconess Medical Center, Boston, MA 02215, USA. |
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| Abstract: | 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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