TY - JOUR
T1 - Impaired tumor necrosis factor-α secretion by CD4 T cells during respiratory syncytial virus bronchiolitis associated with recurrent wheeze
AU - Kitcharoensakkul, Maleewan
AU - Bacharier, Leonard B.
AU - Yin-Declue, Huiqing
AU - Boomer, Jonathan S.
AU - Sajol, Geneline
AU - Leung, Marilyn K.
AU - Wilson, Brad
AU - Schechtman, Kenneth B.
AU - Atkinson, John P.
AU - Green, Jonathan M.
AU - Castro, Mario
N1 - Funding Information:
We are extremely appreciative of the children and their families that participated in the RBEL-II study. The study is supported by the National Heart, Lung, and Blood Institute/National Institutes of Health NIH/NHLBI RO1 HL092486 (LB, MC); U54 HL112303 (JPA); National Institute of General Medical Sciences, National Institutes of Health RO1 GM099111 (JPA); National Institute of Allergy and Infectious Diseases/National Institutes of Health RO1 AI041592 (JPA) U19 AI070489 (MC); and NIH/NCATS UL1 TR000448. The study is supported by the National Heart, Lung, and Blood Institute/National Institutes of Health NIH/NHLBI RO1 HL092486 (LB, MC); U54 HL112303 (JPA); National Institute of General Medical Sciences, National Institutes of Health RO1 GM099111 (JPA); National Institute of Allergy and Infectious Diseases/National Institutes of Health RO1 AI041592 (JPA), U19 AI070489 (MC); and NIH/NCATS UL1 TR000448.
Funding Information:
We are extremely appreciative of the children and their families that participated in the RBEL‐II study. The study is supported by the National Heart, Lung, and Blood Institute/National Institutes of Health NIH/NHLBI RO1 HL092486 (LB, MC); U54 HL112303 (JPA); National Institute of General Medical Sciences, National Institutes of Health RO1 GM099111 (JPA); National Institute of Allergy and Infectious Diseases/National Institutes of Health RO1 AI041592 (JPA) U19 AI070489 (MC); and NIH/NCATS UL1 TR000448. The study is supported by the National Heart, Lung, and Blood Institute/National Institutes of Health NIH/NHLBI RO1 HL092486 (LB, MC); U54 HL112303 (JPA); National Institute of General Medical Sciences, National Institutes of Health RO1 GM099111 (JPA); National Institute of Allergy and Infectious Diseases/National Institutes of Health RO1 AI041592 (JPA), U19 AI070489 (MC); and NIH/NCATS UL1 TR000448.
Publisher Copyright:
© 2019 The Authors. Immunity, Inflammation and Disease published by John Wiley & Sons Ltd.
PY - 2020/3/1
Y1 - 2020/3/1
N2 - 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+CD25hiFoxp3hi) 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+CD25hiFoxp3hi) 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.
AB - 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+CD25hiFoxp3hi) 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+CD25hiFoxp3hi) 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.
KW - Tregs
KW - recurrent wheeze
KW - respiratory syncytial virus bronchiolitis
KW - tumor necrosis factor
UR - http://www.scopus.com/inward/record.url?scp=85078615976&partnerID=8YFLogxK
U2 - 10.1002/iid3.281
DO - 10.1002/iid3.281
M3 - Article
C2 - 31901157
AN - SCOPUS:85078615976
SN - 2050-4527
VL - 8
SP - 30
EP - 39
JO - Immunity Inflammation and Disease
JF - Immunity Inflammation and Disease
IS - 1
ER -