Dataset Information

IL-13-producing BLT1-positive CD8 cells are increased in asthma and are associated with airway obstruction.

ABSTRACT: The role of CD8 T lymphocytes in the pathogenesis of asthma is not well understood. We investigated whether a subset of IL-13-producing BLT1-positive CD8 T lymphocytes are present in asthmatic airways and are associated with impaired lung function.Bronchoalveolar lavage (BAL) cells were obtained from asthmatic (n = 39) and healthy control (n = 28) subjects. Cells were stimulated with phorbol ester and ionomycin in the presence of brefeldin A and stained for CD8, BLT1, and intracellular IL-13. The frequency of IL-13-producing BLT1-positive CD8 T lymphocytes was compared between the two groups and related to lung function, serum IgE levels, and reticular basement membrane (RBM) thickness.A subset of CD8 T lymphocytes expressing BLT1 and producing IL-13 were detected in the airways of all asthmatic subjects. The frequency of this subset among recovered lymphocytes was significantly higher in the airways of asthmatic subjects compared with controls (mean ± SEM: 16.2 ± 1.4 vs 5.3 ± 0.5, respectively, P < 0.001) and correlated positively with serum IgE levels and RBM thickness. More importantly, the frequency of CD8 T lymphocytes co-expressing BLT1 and IL-13 was inversely related to FEV1 and FEF[25-75] percent predicted values (P < 0.001).A subset of CD8 T lymphocytes expressing BLT1 and producing IL-13 is present in the airways of asthmatics. The accumulation of these cells is associated with airway obstruction, suggesting that they may play a significant pathogenic role in bronchial asthma.

SUBMITTER: Dakhama A

PROVIDER: S-EPMC3630251 | biostudies-literature | 2013

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

IL-13-producing BLT1-positive CD8 cells are increased in asthma and are associated with airway obstruction.

Dakhama A A Collins M L ML Ohnishi H H Goleva E E Leung D Y M DY Alam R R Sutherland E R ER Martin R J RJ Gelfand E W EW

Allergy 20130410 5

<h4>Background</h4>The role of CD8 T lymphocytes in the pathogenesis of asthma is not well understood. We investigated whether a subset of IL-13-producing BLT1-positive CD8 T lymphocytes are present in asthmatic airways and are associated with impaired lung function.<h4>Methods</h4>Bronchoalveolar lavage (BAL) cells were obtained from asthmatic (n = 39) and healthy control (n = 28) subjects. Cells were stimulated with phorbol ester and ionomycin in the presence of brefeldin A and stained for CD8 ...[more]

PMID: 23573812

Similar Datasets

Project description:BACKGROUND:Studies have shown that airway obstruction and increased bronchial reactivity are present in early life in children developing asthma, which challenges the dogma that airway inflammation leads to low lung function. Further studies are needed to explore whether low lung function and bronchial hyperreactivity are inherent traits increasing the risk of developing airway inflammation and asthmatic symptoms in order to establish timely primary preventive initiatives. METHODS AND FINDINGS:We investigated 367 (89%) of the 411 children from the at-risk Copenhagen Prospective Studies on Asthma in Childhood 2000 (COPSAC2000) birth cohort born to mothers with asthma, who were assessed by spirometry and bronchial reactivity to methacholine from age 1 month, plethysmography and bronchial reversibility from age 3 years, cold dry air hyperventilation from age 4 years, and exercise challenge at age 7 years. The COPSAC pediatricians diagnosed and treated asthma based on symptom load, response to inhaled corticosteroid, and relapse after treatment withdrawal according to a standardized algorithm. Repeated measures mixed models were applied to analyze lung function trajectories in children with asthma ever or never at age 1 month to 13 years. The number of children ever versus never developing asthma in their first 13 years of life was 97 (27%) versus 270 (73%), respectively. Median age at diagnosis was 2.0 years (IQR 1.2-5.7), and median remission age was 6.2 years (IQR 4.2-7.8). Children with versus without asthma had reduced lung function (z-score difference, forced expiratory volume, -0.31 [95% CI -0.47; -0.15], p < 0.001), increased airway resistance (z-score difference, specific airway resistance, +0.40 [95% CI +0.24; +0.56], p < 0.001), increased bronchial reversibility (difference in change in forced expiratory volume in the first second [?FEV1], +3% [95% CI +2%; +4%], p < 0.001), increased reactivity to methacholine (z-score difference for provocative dose, -0.40 [95% CI -0.58; -0.22], p < 0.001), decreased forced expiratory volume at cold dry air challenge (?FEV1, -4% [95% CI -7%; -1%], p < 0.01), and decreased forced expiratory volume after exercise (?FEV1, -4% [95% CI -7%; -1%], p = 0.02). Both airway obstruction and bronchial hyperreactivity were present before symptom debut, independent of disease duration, and did not improve with symptom remission. The generalizability of these findings may be limited by the high-risk nature of the cohort (all mothers had a diagnosis of asthma), the modest study size, and limited ethnic variation. CONCLUSIONS:Children with asthma at some point at age 1 month to 13 years had airway obstruction and bronchial hyperreactivity before symptom debut, which did not worsen with increased asthma symptom duration or attenuate with remission. This suggests that airway obstruction and bronchial hyperreactivity are stable traits of childhood asthma since neonatal life, implying that symptomatic disease may in part be a consequence of these traits but not their cause.

Dataset Information

IL-13-producing BLT1-positive CD8 cells are increased in asthma and are associated with airway obstruction.

Publications

IL-13-producing BLT1-positive CD8 cells are increased in asthma and are associated with airway obstruction.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets