{"doi":"10.1172/jci169496","title":"KIR-HLA interactions extend human CD8+ T cell lifespan in vivo","abstract":"BACKGROUNDThere is increasing evidence, in transgenic mice and in vitro, that inhibitory killer cell immunoglobulin-like receptors (iKIRs) can modulate T cell responses. Furthermore, we have previously shown that iKIRs are an important determinant of T cell-mediated control of chronic viral infection and that these results are consistent with an increase in the CD8+ T cell lifespan due to iKIR-ligand interactions. Here, we tested this prediction and investigated whether iKIRs affect T cell lifespan in humans in vivo.METHODSWe used stable isotope labeling with deuterated water to quantify memory CD8+ T cell survival in healthy individuals and patients with chronic viral infections.RESULTSWe showed that an individual's iKIR-ligand genotype was a significant determinant of CD8+ T cell lifespan: in individuals with 2 iKIR-ligand gene pairs, memory CD8+ T cells survived, on average, for 125 days; in individuals with 4 iKIR-ligand gene pairs, the memory CD8+ T cell lifespan doubled to 250 days. Additionally, we showed that this survival advantage was independent of iKIR expression by the T cell of interest and, further, that the iKIR-ligand genotype altered the CD8+ and CD4+ T cell immune aging phenotype.CONCLUSIONSTogether, these data reveal an unexpectedly large effect of iKIR genotype on T cell survival.FUNDINGWellcome Trust; Medical Research Council; EU Horizon 2020; EU FP7; Leukemia and Lymphoma Research; National Institute of Health Research (NIHR) Imperial Biomedical Research Centre; Imperial College Research Fellowship; National Institutes of Health; Jefferiss Trust.","journal":"Journal of Clinical Investigation","year":2023,"id":335269,"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":20,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9543,"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":557006,"name":"Ada W. C. Yan","orcid":"0000-0001-7456-339X","position":1,"is_corresponding":false},{"id":488175,"name":"Lies Boelen","orcid":"0000-0003-3786-5545","position":2,"is_corresponding":false},{"id":1064676,"name":"Linda Hadcocks","orcid":"0000-0003-1811-7146","position":3,"is_corresponding":false},{"id":1065195,"name":"Arafa Salam","orcid":null,"position":4,"is_corresponding":false},{"id":1065196,"name":"Daniel Padrosa Gispert","orcid":null,"position":5,"is_corresponding":false},{"id":1065197,"name":"Loiza Spanos","orcid":null,"position":6,"is_corresponding":false},{"id":1064677,"name":"Laura Mora-Bitria","orcid":"0000-0002-0850-1833","position":7,"is_corresponding":false},{"id":505158,"name":"Neda Nemat‐Gorgani","orcid":"0000-0001-9323-8744","position":8,"is_corresponding":false},{"id":505161,"name":"James A. Traherne","orcid":"0000-0002-6003-8559","position":9,"is_corresponding":false},{"id":686733,"name":"Chrissy h. Roberts","orcid":"0000-0003-1064-5980","position":10,"is_corresponding":false},{"id":1065198,"name":"Danai Koftori","orcid":null,"position":11,"is_corresponding":false},{"id":354233,"name":"Graham P. Taylor","orcid":"0000-0002-3773-2390","position":12,"is_corresponding":false},{"id":97496,"name":"Daniel Forton","orcid":"0000-0002-0903-9169","position":13,"is_corresponding":false},{"id":19722,"name":"Paul J. Norman","orcid":"0000-0001-8370-7703","position":14,"is_corresponding":false},{"id":348681,"name":"Steven G. E. Marsh","orcid":"0000-0003-2855-4120","position":15,"is_corresponding":false},{"id":526921,"name":"Robert Busch","orcid":"0000-0002-4132-0751","position":16,"is_corresponding":false},{"id":458787,"name":"Derek C. Macallan","orcid":"0000-0002-3014-7148","position":17,"is_corresponding":false},{"id":458788,"name":"Becca Asquith","orcid":"0000-0002-5911-3160","position":18,"is_corresponding":false},{"id":975725,"name":"Yan Zhang","orcid":"0000-0002-4091-1365","position":0,"is_corresponding":true}],"reference_count":54,"raw_metadata":null,"created_at":"2026-07-19T01:09:58.338267Z","pmid":"37071474","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":[]}