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¹ Department of Medicine and ² Department of Surgery, Harvard Medical School, Transplantation Research Center, Beth Israel Deaconess Medical Center, Boston, MA 02215
³ Boston University Medical Center, Boston, MA 02118
⁴ Department of Medicine, University of Virginia, Charlottesville, VA 22908
⁵ Department of Neurology, Center for Neurological Diseases, Brigham and Women's Hospital, Boston, MA 02115

CORRESPONDENCE Terry B. Strom: tstrom{at}bidmc.harvard.edu OR Simon C. Robson: srobson{at}bidmc.harvard.edu

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.

T.B. Strom and S.C. Robson contributed equally to this paper.

S. Deaglio's present address is Dept. of Genetics, Biology, and Biochemistry and CeRMS, University of Torino Medical School, 10126 Torino, Italy.

This work was presented, in part, at the Keystone Symposium on Regulatory T cells in Vancouver, Canada in February 2007.

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