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We aimed to evaluate the relationships between regulatory T cell (Treg) percentage and cytokine production of in vitro\u2010stimulated CD4+ T cells during acute bronchiolitis and the development of recurrent wheezing in the first 3 years of life.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We obtained peripheral blood from 166 infants hospitalized with their first episode of RSV\u2010confirmed bronchiolitis. Granzyme B (GZB) expression, and interleukin\u201010, interferon\u2010\u03b3, tumor necrosis factor\u2010\u03b1 (TNF\u2010\u03b1), IL\u20104, and IL\u20105 production by in vitro anti\u2010CD3\/CD28\u2010 and anti\u2010CD3\/CD46\u2010activated CD4+ T cells, and percentage of peripheral Treg (CD4+CD25<jats:sup>hi<\/jats:sup>Foxp3<jats:sup>hi<\/jats:sup>) 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.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Sixty\u2010seven percent (n\u2009=\u2009111) of children had wheezing after their initial RSV infection, with 30% having recurrent wheezing. The percentage of peripheral Treg (CD4+CD25<jats:sup>hi<\/jats:sup>Foxp3<jats:sup>hi<\/jats:sup>) cells was not significantly different between the wheezing groups. Decreased TNF\u2010\u03b1 production from anti\u2010CD3\/CD28\u2212 and anti\u2010CD3\/CD46\u2212 activated CD4+ T cells was observed in the recurrent wheezers, compared with nonwheezers (<jats:italic>p<\/jats:italic>\u2009=\u2009.048 and .03, respectively). There were no significant differences in the GZB+ CD4+ T cells and production of other inflammatory cytokines between these groups.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>We demonstrated lower TNF\u2010\u03b1 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.<\/jats:p><\/jats:sec>","DOI":"10.1002\/iid3.281","type":"journal-article","created":{"date-parts":[[2020,1,4]],"date-time":"2020-01-04T12:40:38Z","timestamp":1578141638000},"page":"30-39","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Impaired tumor necrosis factor\u2010\u03b1 secretion by CD4 T cells during respiratory syncytial virus bronchiolitis associated with recurrent wheeze"],"prefix":"10.1002","volume":"8","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1080-4681","authenticated-orcid":false,"given":"Maleewan","family":"Kitcharoensakkul","sequence":"first","affiliation":[{"name":"The Division of Allergy, Immunology and Pulmonary Medicine, Department of Pediatrics, St. Louis Children's Hospital Washington University School of Medicine  St. Louis Missouri"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leonard B.","family":"Bacharier","sequence":"additional","affiliation":[{"name":"The Division of Allergy, Immunology and Pulmonary Medicine, Department of Pediatrics, St. Louis Children's Hospital Washington University School of Medicine  St. Louis Missouri"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huiqing","family":"Yin\u2010Declue","sequence":"additional","affiliation":[{"name":"The Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine Washington University School of Medicine St. Louis Missouri"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jonathan S.","family":"Boomer","sequence":"additional","affiliation":[{"name":"The Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine Washington University School of Medicine St. Louis Missouri"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Geneline","family":"Sajol","sequence":"additional","affiliation":[{"name":"The Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine Washington University School of Medicine St. Louis Missouri"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marilyn K.","family":"Leung","sequence":"additional","affiliation":[{"name":"The Division of Rheumatology, Department of Internal Medicine Washington University School of Medicine St. Louis Missouri"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brad","family":"Wilson","sequence":"additional","affiliation":[{"name":"The Division of Biostatistics Washington University School of Medicine St. Louis Missouri"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kenneth B.","family":"Schechtman","sequence":"additional","affiliation":[{"name":"The Division of Biostatistics Washington University School of 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