{"doi":"10.1172/jci158122","title":"Longitudinal analysis reveals age-related changes in the T cell receptor repertoire of human T cell subsets","abstract":"A diverse T cell receptor (TCR) repertoire is essential for protection against a variety of pathogens, and TCR repertoire size is believed to decline with age. However, the precise size of human TCR repertoires, in both total and subsets of T cells, as well as their changes with age, are not fully characterized. We conducted a longitudinal analysis of the human blood TCRα and TCRβ repertoire of CD4+ and CD8+ T cell subsets using a unique molecular identifier-based (UMI-based) RNA-seq method. Thorough analysis of 1.9 × 108 T cells yielded the lower estimate of TCR repertoire richness in an adult at 3.8 × 108. Alterations of the TCR repertoire with age were observed in all 4 subsets of T cells. The greatest reduction was observed in naive CD8+ T cells, while the greatest clonal expansion was in memory CD8+ T cells, and the highest increased retention of TCR sequences was in memory CD8+ T cells. Our results demonstrated that age-related TCR repertoire attrition is subset specific and more profound for CD8+ than CD4+ T cells, suggesting that aging has a more profound effect on cytotoxic as opposed to helper T cell functions. This may explain the increased susceptibility of older adults to novel infections.","journal":"Journal of Clinical Investigation","year":2022,"id":234442,"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":98,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9127,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2022-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":541095,"name":"Thomas Nguyen","orcid":"0000-0002-7580-1617","position":1,"is_corresponding":false},{"id":542096,"name":"Achouak Achour","orcid":null,"position":2,"is_corresponding":false},{"id":542095,"name":"Annette Ko","orcid":null,"position":3,"is_corresponding":false},{"id":568261,"name":"Jeffrey Cifello","orcid":"0009-0000-6147-2026","position":4,"is_corresponding":false},{"id":415528,"name":"Chen Ling","orcid":"0000-0003-1527-1471","position":5,"is_corresponding":false},{"id":850018,"name":"Jay Sharma","orcid":"0000-0002-0876-7973","position":6,"is_corresponding":false},{"id":850494,"name":"Toyoko Hiroi","orcid":null,"position":7,"is_corresponding":false},{"id":451857,"name":"Yongqing Zhang","orcid":"0000-0003-0581-4882","position":8,"is_corresponding":false},{"id":264193,"name":"Chee W. Chia","orcid":"0000-0003-3218-0141","position":9,"is_corresponding":false},{"id":304885,"name":"William H. Wood","orcid":"0000-0003-0683-8085","position":10,"is_corresponding":false},{"id":692308,"name":"Wells W. Wu","orcid":"0000-0002-6392-2235","position":11,"is_corresponding":false},{"id":264192,"name":"Linda Zukley","orcid":"0000-0003-2677-7590","position":12,"is_corresponding":false},{"id":533429,"name":"Je‐Nie Phue","orcid":"0000-0002-3502-3726","position":13,"is_corresponding":false},{"id":291059,"name":"Kevin G. Becker","orcid":"0000-0002-6794-6656","position":14,"is_corresponding":false},{"id":636550,"name":"Rong‐Fong Shen","orcid":"0000-0002-1963-4033","position":15,"is_corresponding":false},{"id":21956,"name":"Luigi Ferrucci","orcid":"0000-0002-6273-1613","position":16,"is_corresponding":false},{"id":420559,"name":"Nan‐ping Weng","orcid":"0000-0001-8175-8953","position":17,"is_corresponding":false},{"id":445197,"name":"Xiaoping Sun","orcid":"0000-0002-7766-9306","position":0,"is_corresponding":true}],"reference_count":61,"raw_metadata":null,"created_at":"2026-07-19T00:21:36.529874Z","pmid":"35708913","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":[]}