PD-L1 – PD-1 interactions limit effector Treg cell populations at homeostasis and during infection

While much is known about the factors that promote diverse Treg cell responses, less is known about mechanisms that constrain Treg cells. Here we demonstrate phenotypic and transcriptional profiling at homeostasis, which reveals TCR activation promotes a population of Treg cells that display an effector phenotype (eTreg) enriched for production of suppressive proteins such as IL-10 and CTLA-4. However, these eTreg cells express the inhibitory receptor PD-1 and blockade of PD-L1 or loss of PD-1 results in increased eTreg cell activity associated with enhanced homeostatic proliferation and survival. Thus, eTreg cell expression of PD-1 acts as a sensor to rapidly tune the pool of eTreg cells at homeostasis. Overall design: Three to four biological replicates were analyzed for each of 4 conditions (isotype and antibody treatment; conventional and effector Tregs)