T-cell activation during exacerbations: a longitudinal study in refractory asthma

Background: Asthma exacerbations represent the main source of costs and morbidity in asthma care, and drugs specifically designed to prevent exacerbations are needed. A prerequisite is to dispose of a precise knowledge of inflammatory events leading to exacerbations. Objective: To study T-cell activation during exacerbations from severe refractory asthmatics. Methods: Proportions of blood T-cell interleukin (IL)-13, interferon-gamma, IL-4, IL-5, IL-10 production and of CD4+CD25+(high)CD62L+CD45RO+ [T regulatory (Treg)] cells were determined by flow cytometry. Blood cytokine mRNA was studied by reverse transcription-polymerase chain reaction and the respective protein levels were determined by cytokine beads array. Depletion of Treg cells was performed to study their activation. T-cell cytokines were detected in parallel in induced sputum. Results: At baseline, T helper 2 (Th2) cells were increased in asthmatics, whereas T helper 1 (Th1) and Treg T cells were decreased. T helper 2 cells increased before exacerbations, followed by Th1 cells, in blood and induced sputum, albeit Treg cells decreased in parallel with IL-10-producing T cells. Concordant results were found at the mRNA level. The suppressive activity of Treg cells was impaired during exacerbations compared to baseline. Conclusions: New insights are given into pathophysiology of asthma exacerbations: Although at baseline T-cell activation is Th2-biased, a mixed Th1/Th2 activation occurs during exacerbations. The Treg cell deficiency found at baseline in SRA increases during exacerbations.