The A2A Adenosine Receptor regulates T cell effector and memory differentiation (132.13)

Abstract

Abstract The A2A adenosine receptor (A2A AR) plays a critical role in regulating immune system activation and tolerance. We hypothesized that A2AR blockade would enhance T cell responses to viral infection. Indeed, A2A AR-/- T cells demonstrate increased expansion in response to vaccinia infection when measured 5 days after infection, and in co-adoptive transfer experiments A2A AR-/- clonotypic cells out perform their WT clonotypic counterparts. Surprisingly, two weeks post infection such was not case. Instead we found fewer A2A AR-/- clonotypic cells. Interestingly, in spite of the fact that the vaccinia infection is cleared rapidly, the A2A AR-/- clonotypic cells appeared “exhausted” displaying markers of chronic activation and the inhibitory receptor PD-1. Unlike what was seen with the A2A AR-/- T cells, pharmacologic treatment of WT mice with an A2A AR antagonist during the 5 days post infection led to a marked increase recall potency. Overall, our data demonstrate a previously unappreciated role for adenosine and the A2aR in regulating effector cell expansion and memory differentiation. Consequently, pharmacologic A2A AR blockade selectively during the perivaccine period can lead to both enhanced effector and memory responses.