Adenosine generation catalyzed by CD39 and CD73 expressed on regulatory T cells mediates immune suppression.
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
Journal of Experimental Medicine | Published : 2007
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..View full abstract