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J Exp Med. 2007 Jun 11;204(6):1257-65. Epub 2007 May 14.

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

Author information

1
Department of Medicine, Harvard Medical School, Transplantation Research Center, Beth Israel Deaconess Medical Center, Boston, MA 02215, USA.

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.

PMID:
17502665
PMCID:
PMC2118603
DOI:
10.1084/jem.20062512
[Indexed for MEDLINE]
Free PMC Article

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