{"doi":"10.1002/iid3.281","title":"Impaired tumor necrosis factor‐α secretion by CD4 T cells during respiratory syncytial virus bronchiolitis associated with recurrent wheeze","abstract":"Abstract Background Infants with severe respiratory syncytial virus (RSV) bronchiolitis have an increased risk of recurrent wheezing and asthma. We aimed to evaluate the relationships between regulatory T cell (Treg) percentage and cytokine production of in vitro‐stimulated CD4+ T cells during acute bronchiolitis and the development of recurrent wheezing in the first 3 years of life. Methods We obtained peripheral blood from 166 infants hospitalized with their first episode of RSV‐confirmed bronchiolitis. Granzyme B (GZB) expression, and interleukin‐10, interferon‐γ, tumor necrosis factor‐α (TNF‐α), IL‐4, and IL‐5 production by in vitro anti‐CD3/CD28‐ and anti‐CD3/CD46‐activated CD4+ T cells, and percentage of peripheral Treg (CD4+CD25 hi Foxp3 hi ) cells were measured by flow cytometry. Wheezing was assessed every 6 months. Recurrent wheezing was defined as three or more episodes following the initial RSV bronchiolitis. Results Sixty‐seven percent (n = 111) of children had wheezing after their initial RSV infection, with 30% having recurrent wheezing. The percentage of peripheral Treg (CD4+CD25 hi Foxp3 hi ) cells was not significantly different between the wheezing groups. Decreased TNF‐α production from anti‐CD3/CD28− and anti‐CD3/CD46− activated CD4+ T cells was observed in the recurrent wheezers, compared with nonwheezers ( p = .048 and .03, respectively). There were no significant differences in the GZB+ CD4+ T cells and production of other inflammatory cytokines between these groups. Conclusions We demonstrated lower TNF‐α production by in vitro stimulated CD4+ T cells during severe RSV bronchiolitis in children that subsequently developed recurrent wheezing, compared with children with no subsequent wheeze. These findings support the role of CD4+ T cell immunity in the development of subsequent wheezing in these children.","journal":"Immunity Inflammation and Disease","year":2020,"id":89669,"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":8,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9568,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2020-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":110400,"name":"Leonard B. Bacharier","orcid":"0000-0003-0432-2704","position":1,"is_corresponding":false},{"id":414934,"name":"Huiqing Yin‐Declue","orcid":null,"position":2,"is_corresponding":false},{"id":454016,"name":"Jonathan Boomer","orcid":null,"position":3,"is_corresponding":false},{"id":454017,"name":"Geneline Sajol","orcid":null,"position":4,"is_corresponding":false},{"id":454018,"name":"Marilyn K. Leung","orcid":null,"position":5,"is_corresponding":false},{"id":454019,"name":"Brad Wilson","orcid":null,"position":6,"is_corresponding":false},{"id":243672,"name":"Kenneth B. Schechtman","orcid":null,"position":7,"is_corresponding":false},{"id":230292,"name":"John Atkinson","orcid":"0000-0003-2809-9308","position":8,"is_corresponding":false},{"id":453084,"name":"Jonathan M. Green","orcid":"0000-0002-7449-4387","position":9,"is_corresponding":false},{"id":281776,"name":"Mario Castro","orcid":"0000-0001-6328-8994","position":10,"is_corresponding":false},{"id":280626,"name":"Maleewan Kitcharoensakkul","orcid":"0000-0002-1080-4681","position":0,"is_corresponding":true}],"reference_count":49,"raw_metadata":null,"created_at":"2026-07-18T22:02:27.195966Z","pmid":"31901157","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":[]}