{"doi":"10.1084/jem.20182232","title":"PD-1 restraint of regulatory T cell suppressive activity is critical for immune tolerance","abstract":"Inhibitory signals through the PD-1 pathway regulate T cell activation, T cell tolerance, and T cell exhaustion. Studies of PD-1 function have focused primarily on effector T cells. Far less is known about PD-1 function in regulatory T (T reg) cells. To study the role of PD-1 in T reg cells, we generated mice that selectively lack PD-1 in T reg cells. PD-1-deficient T reg cells exhibit an activated phenotype and enhanced immunosuppressive function. The in vivo significance of the potent suppressive capacity of PD-1-deficient T reg cells is illustrated by ameliorated experimental autoimmune encephalomyelitis (EAE) and protection from diabetes in nonobese diabetic (NOD) mice lacking PD-1 selectively in T reg cells. We identified reduced signaling through the PI3K-AKT pathway as a mechanism underlying the enhanced suppressive capacity of PD-1-deficient T reg cells. Our findings demonstrate that cell-intrinsic PD-1 restraint of T reg cells is a significant mechanism by which PD-1 inhibitory signals regulate T cell tolerance and autoimmunity.","journal":"The Journal of Experimental Medicine","year":2020,"id":49378,"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":262,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9467,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2020-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":69338,"name":"Juhi R. Kuchroo","orcid":"0000-0001-9033-3420","position":1,"is_corresponding":false},{"id":108669,"name":"Peter T. Sage","orcid":"0000-0002-7287-0326","position":2,"is_corresponding":false},{"id":237743,"name":"Dan Liang","orcid":"0000-0001-7363-4803","position":3,"is_corresponding":false},{"id":237744,"name":"Loise M. Francisco","orcid":"0000-0003-2948-1736","position":4,"is_corresponding":false},{"id":237745,"name":"Jessica N. Buck","orcid":"0000-0002-7586-364X","position":5,"is_corresponding":false},{"id":237746,"name":"Youg Raj Thaker","orcid":"0000-0002-6496-1017","position":6,"is_corresponding":false},{"id":237747,"name":"Qianxia Zhang","orcid":"0000-0002-2885-2147","position":7,"is_corresponding":false},{"id":237748,"name":"Shannon McArdel","orcid":"0000-0001-6602-1486","position":8,"is_corresponding":false},{"id":108664,"name":"Vikram R. Juneja","orcid":"0000-0001-6011-6417","position":9,"is_corresponding":false},{"id":237749,"name":"Sun Jung Lee","orcid":"0000-0003-4423-2447","position":10,"is_corresponding":false},{"id":237750,"name":"Scott B. Lovitch","orcid":"0000-0001-9013-0105","position":11,"is_corresponding":false},{"id":40506,"name":"Christine G. Lian","orcid":"0000-0003-4626-1612","position":12,"is_corresponding":false},{"id":237751,"name":"George F. Murphy","orcid":"0000-0002-3909-1160","position":13,"is_corresponding":false},{"id":52067,"name":"Bruce R. Blazar","orcid":"0000-0002-9608-9841","position":14,"is_corresponding":false},{"id":109278,"name":"Dario A.A. Vignali","orcid":"0000-0002-2771-5992","position":15,"is_corresponding":false},{"id":4539,"name":"Gordon J. Freeman","orcid":"0000-0002-7210-5616","position":16,"is_corresponding":false},{"id":4542,"name":"Arlene H. Sharpe","orcid":"0000-0002-9736-2109","position":17,"is_corresponding":false},{"id":237742,"name":"Catherine L. Tan","orcid":"0000-0002-8736-9550","position":0,"is_corresponding":true}],"reference_count":76,"raw_metadata":null,"created_at":"2026-07-18T20:36:25.163232Z","pmid":"33045061","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":[]}