title: Adenosine generation catalyzed by CD39 and CD73 expressed on regulatory T cells mediates immune suppression.
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.
authors.affiliation: Department of Medicine, Harvard Medical School, Transplantation Research Center, Beth Israel Deaconess Medical Center, Boston, MA 02215, USA.
authors.forename: Silvia
authors.initials: S
authors.lastname: Deaglio
authors.forename: Karen M
authors.initials: KM
authors.lastname: Dwyer
authors.forename: Wenda
authors.initials: W
authors.lastname: Gao
authors.forename: David
authors.initials: D
authors.lastname: Friedman
authors.forename: Anny
authors.initials: A
authors.lastname: Usheva
authors.forename: Anna
authors.initials: A
authors.lastname: Erat
authors.forename: Jiang-Fan
authors.initials: JF
authors.lastname: Chen
authors.forename: Keiichii
authors.initials: K
authors.lastname: Enjyoji
authors.forename: Joel
authors.initials: J
authors.lastname: Linden
authors.forename: Mohamed
authors.initials: M
authors.lastname: Oukka
authors.forename: Vijay K
authors.initials: VK
authors.lastname: Kuchroo
authors.forename: Terry B
authors.initials: TB
authors.lastname: Strom
authors.forename: Simon C
authors.initials: SC
authors.lastname: Robson
mesh_terms: 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
chemical_list: D015703:Antigens, CD; D015720:5'-Nucleotidase; D001081:Apyrase; C067869:CD39 antigen; D000241:Adenosine