Extracellular adenosine production is essential for Treg‐mediated Th cell suppression

Background: Adenosine is an important inflammatory mediator that suppresses proliferation and cytokine production in helper T cells (Th). Two enzymes, CD39 and CD73, expressed on the surface of several cell types including Treg, synthesize adenosine. Expression of these enzymes on Tregs is suggested to play a role in their suppressive ability. Methods: In order to determine whether CD73 activity is involved in Treg‐mediated suppression, we assessed the ability of Treg from CD73 −/− mice to suppress proliferation of wildtype and CD73 −/− effector T cells (Teff) in vitro . Cytokine expression was examined in Th cells from wildtype and CD73 −/− mice stimulated in vitro . To test the function of CD73 on Treg in vivo , Treg from CD73 −/− mice were adoptively transferred with wildtype Teff into RAG1 −/− recipients. Results: CD73 −/− Treg were unable to suppress proliferation of either wildtype or CD73 −/− effector T cells in vitro . In addition, production of inflammatory cytokines by CD73 −/− Th cells was significantly greater than wildtype. Adoptive transfer of Treg from CD73 −/− mice attenuated colitis to a lesser degree than wildtype Treg. Conclusions: These data indicate that extracellular adenosine production by CD73 plays an important role in suppressing Th cell proliferation and inflammatory cytokine production in vitro and inflammation in vivo . Supported by NIH R21 AI069880 and T32 AI007496‐12.