{"doi":"10.4049/immunohorizons.2300094","title":"PD-1 Impairs CD8+ T Cell Granzyme B Production in Aged Mice during Acute Viral Respiratory Infection","abstract":"CD8+ T cell dysfunction contributes to severe respiratory viral infection outcomes in older adults. CD8+ T cells are the primary cell type responsible for viral clearance. With increasing age, CD8+ T cell function declines in conjunction with an accumulation of cytotoxic tissue-resident memory (TRM) CD8+ T cells. We sought to elucidate the role of PD-1 signaling on aged CD8+ T cell function and accumulation of CD8+ TRM cells during acute viral respiratory tract infection, given the importance of PD-1 regulating CD8+ T cells during acute and chronic infections. PD-1 blockade or genetic ablation in aged mice yielded improved CD8+ T cell granzyme B production comparable to that in young mice during human metapneumovirus and influenza viral infections. Syngeneic transplant and adoptive transfer strategies revealed that improved granzyme B production in aged Pdcd1-/- CD8+ T cells was primarily cell intrinsic because aged wild-type CD8+ T cells did not have increased granzyme B production when transplanted into a young host. PD-1 signaling promoted accumulation of cytotoxic CD8+ TRM cells in aged mice. PD-1 blockade of aged mice during rechallenge infection resulted in improved clinical outcomes that paralleled reduced accumulation of CD8+ TRM cells. These findings suggest that PD-1 signaling impaired CD8+ T cell granzyme B production and contributed to CD8+ TRM cell accumulation in the aged lung. These findings have implications for future research investigating PD-1 checkpoint inhibitors as a potential therapeutic option for elderly patients with severe respiratory viral infections.","journal":"ImmunoHorizons","year":2023,"id":371870,"datarank":0.3842450294462831,"base_score":1.9459101490553132,"endowment":1.9459101490553132,"self_citation_contribution":0.29188652235829704,"citation_network_contribution":0.09235850708798604,"self_endowment_contribution":0.29188652235829704,"citer_contribution":0.09235850708798604,"corpus_percentile":null,"corpus_rank":null,"citation_count":6,"citer_count":6,"citers_with_citation_signal":4,"citers_with_endowment":4,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9495,"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":327170,"name":"Danielle Antos","orcid":"0000-0002-8451-0600","position":1,"is_corresponding":false},{"id":780746,"name":"Taylor Eddens","orcid":"0000-0003-2969-3624","position":2,"is_corresponding":false},{"id":759599,"name":"Sara Walters","orcid":"0009-0003-6873-5943","position":3,"is_corresponding":false},{"id":480169,"name":"Monika Johnson","orcid":null,"position":4,"is_corresponding":false},{"id":315201,"name":"Tim D. Oury","orcid":"0000-0002-4253-3214","position":5,"is_corresponding":false},{"id":573677,"name":"Rachel A. Gottschalk","orcid":"0000-0002-5248-8816","position":6,"is_corresponding":false},{"id":536810,"name":"John J. Erickson","orcid":"0000-0001-6189-9302","position":7,"is_corresponding":false},{"id":236968,"name":"John V. Williams","orcid":"0000-0001-8377-5175","position":8,"is_corresponding":false},{"id":657355,"name":"Olivia B. Parks","orcid":"0000-0003-1131-9407","position":0,"is_corresponding":true}],"reference_count":54,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-07-19T01:15:49.453761Z","pmid":"38015461","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":[]}