Regulation of human and mouse bystander T cell activation responses by PD-1.
oregon; chiles; Adaptive immunity; Cytokines; Immunology; T cells; Humans; Animals; Mice; Programmed Cell Death 1 Receptor; Lymphocyte Activation; Cytokines; Memory T Cells; Phenotype
Bystander activation of memory T cells occurs via cytokine signaling alone in the absence of T cell receptor (TCR) signaling and provides a means of amplifying T cell effector responses in an antigen-nonspecific manner. While the role of Programmed Cell Death Protein 1 (PD-1) on antigen-specific T cell responses is extensively characterized, its role in bystander T cell responses is less clear. We examined the role of the PD-1 pathway during human and mouse non-antigen-specific memory T cell bystander activation and observed that PD-1+ T cells demonstrated less activation and proliferation than activated PD-1- populations in vitro. Higher activation and proliferative responses were also observed in the PD-1- memory population in both mice and patients with cancer receiving high-dose IL-2, mirroring the in vitro phenotypes. This inhibitory effect of PD-1 could be reversed by PD-1 blockade in vivo or observed using memory T cells from PD-1-/- mice. Interestingly, increased activation through abrogation of PD-1 signaling in bystander-activated T cells also resulted in increased apoptosis due to activation-induced cell death (AICD) and eventual T cell loss in vivo. These results demonstrate that the PD-1/PD-Ligand 1 (PD-L1) pathway inhibited bystander-activated memory T cell responses but also protected cells from AICD.
Le, Catherine T; Vick, Logan V; Collins, Craig; Dunai, Cordelia; Sheng, Michael K; Khuat, Lam T; Barao, Isabel; Judge, Sean J; Aguilar, Ethan G; Curti, Brendan; Dave, Maneesh; Longo, Dan L; Blazar, Bruce R; Canter, Robert J; Monjazeb, Arta M; and Murphy, William J, "Regulation of human and mouse bystander T cell activation responses by PD-1." (2023). Articles, Abstracts, and Reports. 7848.