Decreased CTLA4+ and Foxp3+ CD25highCD4+ Cells in Induced Sputum from Patients with Mild Atopic Asthma

Background: Details of the comparisons between airway and peripheral blood regulatory T cells (Tregs) in patients with atopic asthma are still unclear. The objective of this study is to investigate the profiles of both airway and circulating Tregs in atopic asthma. Methods: We measured the numbers of Tregs and eosinophils in induced sputum and peripheral blood in 28 patients with mild atopic asthma and compared these with numbers in 18 healthy controls. The frequency (%) of Tregs (surface CTLA4(+), intracellular Foxp3(+), and CTLA4(+)Foxp3(+) on CD25(high)CD4(+) T cells) in sputum and blood was determined by intracellular 5-color flow cytometry. We also correlated the numbers with the level of airway hyperresponsiveness (AHR) in asthmatics. Results: The mean frequencies of cells expressing CTLA4(+) (19.4 +/- 2.1%, p = 0.075), Foxp(3+) (16.4 +/- 3.3%, p = 0.001), and CTLA4(+)Foxp3(+) (7.0 +/- 1.1%, p = 0.008) in induced sputum from asthmatics were significantly lower than controls (27.2 +/- 3.7%, 37.4 +/- 4.7%, and 18.2 +/- 3.6%, respectively), whereas in peripheral blood, there was no inter-group difference in the frequencies of cells expressing CTLA4(+) (7.1 +/- 1.5% vs 5.7 +/- 1.7%, p > 0.05), Foxp3(+) (35.7 +/- 3.2% vs 21.1 +/- 3.9%, p > 0.05), and CTLA4(+)Foxp3(+) (6.6 +/- 1.5% vs 4.2 +/- 1.0%, p > 0.05). Moreover, the frequency of CD25(high)CD4(+) cells expressing CTLA4(+), but not Foxp3(+), in induced sputum was associated with AHR (r = 0.60, p = 0.009) and airway eosinophilic inflammation (r = -0.60, p = 0.008) in asthmatics. Conclusions: Airway, but not circulating, Tregs are decreased in mild atopic asthmatics, and are negatively correlated to an increase of airway eosinophilic inflammation and AHR.