{"doi":"10.3389/fragi.2021.719342","title":"Aging and CMV Infection Affect Pre-existing SARS-CoV-2-Reactive CD8+ T Cells in Unexposed Individuals","abstract":"Age is a major risk factor for COVID-19 severity, and T cells play a central role in anti-SARS-CoV-2 immunity. Because SARS-CoV-2-cross-reactive T cells have been detected in unexposed individuals, we investigated the age-related differences in pre-existing SARS-CoV-2-reactive T cells. SARS-CoV-2-reactive CD4 + T cells from young and elderly individuals were mainly detected in the central memory fraction and exhibited similar functionalities and numbers. Naïve-phenotype SARS-CoV-2-reactive CD8 + T cell populations decreased markedly in the elderly, while those with terminally differentiated and senescent phenotypes increased. Furthermore, senescent SARS-CoV-2-reactive CD8 + T cell populations were higher in cytomegalovirus seropositive young individuals compared to seronegative ones. Our findings suggest that age-related differences in pre-existing SARS-CoV-2-reactive CD8 + T cells may explain the poor outcomes in elderly patients and that cytomegalovirus infection is a potential factor affecting CD8 + T cell immunity against SARS-CoV-2. Thus, this study provides insights for developing effective therapeutic and vaccination strategies for the elderly.","journal":"Frontiers in Aging","year":2021,"id":174675,"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":23,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9562,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2021-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":714267,"name":"Rui Zhang","orcid":"0000-0003-4343-8750","position":1,"is_corresponding":false},{"id":350510,"name":"Hideki Ueno","orcid":"0000-0001-7747-0738","position":2,"is_corresponding":false},{"id":714268,"name":"Takuya Yamamoto","orcid":"0000-0002-0022-3947","position":3,"is_corresponding":false},{"id":103766,"name":"Daniela Weiskopf","orcid":"0000-0003-2968-7371","position":4,"is_corresponding":false},{"id":714269,"name":"Miki Nagao","orcid":"0000-0002-8886-6145","position":5,"is_corresponding":false},{"id":35714,"name":"Shinya Yamanaka","orcid":"0009-0003-1393-0987","position":6,"is_corresponding":false},{"id":714270,"name":"Yoko Hamazaki","orcid":"0000-0002-3911-5708","position":7,"is_corresponding":false},{"id":714266,"name":"Norihide Jo","orcid":"0000-0002-9661-4546","position":0,"is_corresponding":true}],"reference_count":72,"raw_metadata":null,"created_at":"2026-07-18T23:47:06.584146Z","pmid":"35822004","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":[]}