Adenosine Generation Catalyzed by CD39 and CD73 Expressed on Regulatory T Cells Mediates Immune Suppression

Overview

Journal J Exp Med

Specialties Allergy & Immunology
General Medicine

Date 2007 May 16

PMID 17502665

Citations 1170

Authors

Silvia Deaglio

Karen M Dwyer

Wenda Gao

David Friedman

Anny Usheva

Anna Erat

Jiang-Fan Chen

Keiichii Enjyoji

Joel Linden

Mohamed Oukka

Vijay K Kuchroo

Terry B Strom

Simon C Robson

Affiliations

Soon will be listed here.

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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