{"doi":"10.1172/jci.insight.173287","title":"Regulation of human and mouse bystander T cell activation responses by PD-1","abstract":"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.","journal":"JCI Insight","year":2023,"id":343301,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":14,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9512,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2023-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":288709,"name":"Logan V. Vick","orcid":"0009-0006-9778-0120","position":1,"is_corresponding":false},{"id":750445,"name":"Craig Collins","orcid":null,"position":2,"is_corresponding":false},{"id":262401,"name":"Cordelia Dunai","orcid":"0000-0001-5799-2387","position":3,"is_corresponding":false},{"id":1081344,"name":"Michael K. Sheng","orcid":null,"position":4,"is_corresponding":false},{"id":262404,"name":"Lam T. Khuat","orcid":"0000-0002-4223-8805","position":5,"is_corresponding":false},{"id":422964,"name":"Isabel Barão","orcid":null,"position":6,"is_corresponding":false},{"id":262400,"name":"Sean J. Judge","orcid":"0000-0002-1842-9468","position":7,"is_corresponding":false},{"id":262402,"name":"Ethan G. Aguilar","orcid":"0000-0002-3600-0913","position":8,"is_corresponding":false},{"id":425698,"name":"Brendan D. Curti","orcid":"0000-0003-3948-2708","position":9,"is_corresponding":false},{"id":331473,"name":"Maneesh Dave","orcid":"0000-0002-4068-6700","position":10,"is_corresponding":false},{"id":262406,"name":"Dan L. Longo","orcid":"0000-0002-5850-5998","position":11,"is_corresponding":false},{"id":52067,"name":"Bruce R. Blazar","orcid":"0000-0002-9608-9841","position":12,"is_corresponding":false},{"id":262409,"name":"Robert J. Canter","orcid":"0000-0002-3331-5418","position":13,"is_corresponding":false},{"id":259311,"name":"Arta M. Monjazeb","orcid":"0000-0001-5175-8004","position":14,"is_corresponding":false},{"id":259312,"name":"William J. Murphy","orcid":"0000-0002-2793-401X","position":15,"is_corresponding":false},{"id":323876,"name":"Catherine T. Le","orcid":"0000-0002-0175-570X","position":0,"is_corresponding":true}],"reference_count":41,"raw_metadata":null,"created_at":"2026-07-19T01:11:21.758449Z","pmid":"37737264","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}