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Impaired tumor necrosis factor‐α secretion by CD4 T cells during respiratory syncytial virus bronchiolitis associated with recurrent wheeze
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 bronchi...
Autores principales: | , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
John Wiley and Sons Inc.
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7016853/ https://www.ncbi.nlm.nih.gov/pubmed/31901157 http://dx.doi.org/10.1002/iid3.281 |
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author | 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 |
author_facet | 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 |
author_sort | Kitcharoensakkul, Maleewan |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-7016853 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | John Wiley and Sons Inc. |
record_format | MEDLINE/PubMed |
spelling | pubmed-70168532020-03-06 Impaired tumor necrosis factor‐α secretion by CD4 T cells during respiratory syncytial virus bronchiolitis associated with recurrent wheeze 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 Immun Inflamm Dis Original Research 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. John Wiley and Sons Inc. 2020-01-04 /pmc/articles/PMC7016853/ /pubmed/31901157 http://dx.doi.org/10.1002/iid3.281 Text en © 2019 The Authors. Immunity, Inflammation and Disease published by John Wiley & Sons Ltd. This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Original Research 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 Impaired tumor necrosis factor‐α secretion by CD4 T cells during respiratory syncytial virus bronchiolitis associated with recurrent wheeze |
title | Impaired tumor necrosis factor‐α secretion by CD4 T cells during respiratory syncytial virus bronchiolitis associated with recurrent wheeze |
title_full | Impaired tumor necrosis factor‐α secretion by CD4 T cells during respiratory syncytial virus bronchiolitis associated with recurrent wheeze |
title_fullStr | Impaired tumor necrosis factor‐α secretion by CD4 T cells during respiratory syncytial virus bronchiolitis associated with recurrent wheeze |
title_full_unstemmed | Impaired tumor necrosis factor‐α secretion by CD4 T cells during respiratory syncytial virus bronchiolitis associated with recurrent wheeze |
title_short | Impaired tumor necrosis factor‐α secretion by CD4 T cells during respiratory syncytial virus bronchiolitis associated with recurrent wheeze |
title_sort | impaired tumor necrosis factor‐α secretion by cd4 t cells during respiratory syncytial virus bronchiolitis associated with recurrent wheeze |
topic | Original Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7016853/ https://www.ncbi.nlm.nih.gov/pubmed/31901157 http://dx.doi.org/10.1002/iid3.281 |
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