PD-1 restricts the development and effector function of tissue regulatory T cells in experimental autoimmune encephalomyelitis

PD-1 restricts T cell effector functions, regulates T cell tolerance, and maintains immune homeostasis, thereby playing pivotal roles in cancer, autoimmune and infectious diseases. Our studies and others show that PD-1 can restrain Treg suppressive function in autoimmunity and cancer. Here, we investigate the role of Treg intrinsic PD-1 in regulating pathogenic and protective CD4+ T cell responses in experimental autoimmune encephalomyelitis (EAE) by inducing PD-1 deletion on FoxP3+ cells prior to disease development. This deletion of PD-1 only in Treg protects mice from severe disease, and both flow cytometry and transcriptional analysis of central nervous system (CNS) CD4+ T cells show enrichment of tissue effector Treg (eTreg) subsets at peak of disease. We find that PD-1 restrains the generation and suppressive function of these effector Treg. This tissue eTreg signature is also observed in human and mouse Treg subsets from the tumor microenvironment, and are potent suppressor populations. Further studies are underway to determine how PD-1 impacts TCR signaling and FoxP3 transcriptional co-activators in Treg cells. Our study provides deeper insights into how PD-1 regulates T cell tolerance, underscoring the important role of PD-1 in regulating Treg differentiation and suppressive function during autoimmune diseases, and provide mechanistic insights for PD-1 modulation in cancer and autoimmunity. Supported by NIH P01AI108545