Impaired tumor necrosis factor‐α secretion by CD4 T cells during respiratory syncytial virus bronchiolitis associated with recurrent wheeze. Issue 1 (4th January 2020)

• Record Type: Journal Article
• Authors: Kitcharoensakkul, Maleewan; Bacharier, Leonard B.; Yin‐Declue, Huiqing; Boomer, Jonathan S.; Sajol, Geneline; Leung, Marilyn K.; Wilson, Brad; Schechtman, Kenneth B.; Atkinson, John P.; Green, Jonathan M.; Castro, Mario
• Is Part Of: Immunity, inflammation and disease. Volume 8:Issue 1(2020)
• Page Start: 30
• Page End: 39
• Publication Date: 2020-01-04
• Subjects: recurrent wheeze -- respiratory syncytial virus bronchiolitis -- Tregs -- tumor necrosis factor; Immunology -- Periodicals; Immunity -- Periodicals; Inflammation -- Periodicals; 616.079
• DOI: 10.1002/iid3.281
• Languages: English
• ISSNs: 2050-4527

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. Abstract : Infants with severe respiratory syncytial virus (RSV) bronchiolitis have increased risks of recurrent wheezing and asthma. We demonstrated lower tumor necrosis factor‐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.