Adenosine generation catalyzed by CD39 and CD73 expressed on regulatory T cells mediates immune suppression.
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.
Deaglio
Silvia
S
Department of Medicine, Harvard Medical School, Transplantation Research Center, Beth Israel Deaconess Medical Center, Boston, MA 02215, USA.
Dwyer
Karen M
KM
Gao
Wenda
W
Friedman
David
D
Usheva
Anny
A
Erat
Anna
A
Chen
Jiang-Fan
JF
Enjyoji
Keiichii
K
Linden
Joel
J
Oukka
Mohamed
M
Kuchroo
Vijay K
VK
Strom
Terry B
TB
Robson
Simon C
SC
D015720:5'-Nucleotidase / Q000378:metabolism*; D000241:Adenosine / Q000096:biosynthesis*; D000818:Animals; D015703:Antigens, CD / Q000378:metabolism*; D001081:Apyrase / Q000378:metabolism*; D007165:Immunosuppression Therapy; D051379:Mice; D008810:Mice, Inbred C57BL; D016133:Polymerase Chain Reaction; D050378:T-Lymphocytes, Regulatory / Q000276:immunology* / Q000378:metabolism
D015703:Antigens, CD; D015720:5'-Nucleotidase; D001081:Apyrase; C067869:CD39 antigen; D000241:Adenosine