Quantitative and functional impairment of pulmonary CD4+CD25hi regulatory T cells in pediatric asthma

BackgroundAsthma is characterized by a TH2 immune response. CD4+CD25hi regulatory T cells (Tregs) have been proposed to prevent allergic diseases through suppression of TH2 responses.ObjectiveWe sought to investigate the role of CD4+CD25hi T cells in children with asthma.MethodsCD4+CD25hi Tregs and forkhead/winged-helix transcription factor FOXP3 mRNA levels were quantified in peripheral blood and bronchoalveolar lavage fluid (BALF) of 18 children with asthma, 10 children with chronic cough, and 13 control subjects without lung diseases. CD4+CD25hi T cells were isolated from peripheral blood and BALF of asthmatic patients and control subjects, and their capacity to suppress proliferation and cytokine/chemokine production of autologous responder T cells was analyzed.ResultsCD4+CD25hi T cells were decreased in BALF of asthmatic children compared with values in children with cough or control subjects. In children with asthma, inhaled corticosteroid treatment was associated with increased percentages of CD4+CD25hi T cells in peripheral blood and BALF. Isolated BALF and peripheral blood CD4+CD25hi T cells from nonasthmatic subjects suppressed proliferation and cytokine/chemokine production by CD4+CD25− responder T cells. BALF CD4+CD25hi T cells from asthmatic subjects failed to suppress proliferation and production of TH2-associated cytokines and chemokines by CD4+CD25− responder T cells, which was restored after use of inhaled corticosteroids.ConclusionThese findings provide the first evidence that pulmonary CD4+CD25hi Tregs are impaired in pediatric asthma.Clinical implicationsPulmonary Tregs might represent a therapeutic target in pediatric asthma.