{"doi":"10.3389/fragi.2022.1098200","title":"NK- and T-cell granzyme B and K expression correlates with age, CMV infection and influenza vaccine-induced antibody titres in older adults","abstract":"Granzymes are a family of serine-proteases that act as critical mediators in the cytolytic and immunomodulatory activities of immune cells such as CD8 + T-cells and natural killer (NK) cells. Previous work indicates that both granzyme B (GZB) and K (GZK) are increased with age in CD8 + T-cells, and in the case of GZB, contribute to dysfunctional immune processes observed in older adults. Here, we sought to determine how GZB and GZK expression in NK-cells, and CD4 + , CD8 + , and gamma-delta T-cells, quantified in terms of positive cell frequency and mean fluorescence intensity (MFI), differed with age, age-related health-traits and the antibody response to high-dose influenza vaccine. We found that the frequency and MFI of GZB-expressing NK-cells, and CD8 + and Vδ1+ T-cells, and GZK-expressing CD8 + T-cells was significantly higher in older (66–97 years old; n = 75) vs. younger (24–37 years old; n = 10) adults by up to 5-fold. There were no significant associations of GZB/GZK expression with sex, frailty or plasma levels of TNF or IL-6 in older adults, but those who were seropositive for cytomegalovirus (CMV) exhibited significantly higher frequencies of GZB+ NK-cells, and CD4 + , CD8 + and Vδ1+ T-cells, and GZK+ CD8 + T-cells (Cohen’s d = .5–1.5). Pre-vaccination frequencies of GZB+ NK-cells were positively correlated with vaccine antibody responses against A/H3N2 (d = .17), while the frequencies of GZK+ NK and CD8 + T-cells were inversely associated with A/H1N1 (d = −0.18 to −0.20). Interestingly, GZK+ NK-cell frequency was inversely correlated with pre-vaccination A/H1N1 antibody titres, as well as those measured over the previous 4 years, further supporting a role for this subset in influencing vaccine antibody-responses. These findings further our understanding of how granzyme expression in different lymphoid cell-types may change with age, while suggesting that they influence vaccine responsiveness in older adults.","journal":"Frontiers in Aging","year":2023,"id":343776,"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":13,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9589,"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":703539,"name":"Émilie Picard","orcid":"0000-0002-2689-0510","position":1,"is_corresponding":false},{"id":253998,"name":"Melissa K. Andrew","orcid":"0000-0001-7514-8972","position":2,"is_corresponding":false},{"id":253999,"name":"Laura Haynes","orcid":"0000-0002-5006-3339","position":3,"is_corresponding":false},{"id":435936,"name":"Mark Loeb","orcid":"0000-0003-2315-5390","position":4,"is_corresponding":false},{"id":106960,"name":"Graham Pawelec","orcid":"0000-0002-3600-0163","position":5,"is_corresponding":false},{"id":225893,"name":"George A. Kuchel","orcid":"0000-0001-8387-7040","position":6,"is_corresponding":false},{"id":253997,"name":"Chris P. Verschoor","orcid":"0000-0001-6190-2655","position":0,"is_corresponding":true}],"reference_count":52,"raw_metadata":null,"created_at":"2026-07-19T01:11:26.556051Z","pmid":"36685324","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":[]}