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T‐cell activation during exacerbations: a longitudinal study in refractory asthma
Author(s) -
Mamessier E.,
Nieves A.,
Lorec A.M.,
Dupuy P.,
Pinot D.,
Pinet C.,
Vervloet D.,
Magnan A.
Publication year - 2008
Publication title -
allergy
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.363
H-Index - 173
eISSN - 1398-9995
pISSN - 0105-4538
DOI - 10.1111/j.1398-9995.2008.01687.x
Subject(s) - immunology , medicine , sputum , il 2 receptor , cytokine , asthma , flow cytometry , t cell , immune system , pathology , tuberculosis
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‐γ, 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.