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.
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.
Authors: Cyrille Mionnet; Vanessa Buatois; Akira Kanda; Valerie Milcent; Sebastien Fleury; David Lair; Marie Langelot; Yannick Lacoeuille; Edith Hessel; Robert Coffman; Antoine Magnan; David Dombrowicz; Nicolas Glaichenhaus; Valerie Julia Journal: Nat Med Date: 2010-10-31 Impact factor: 53.440
Authors: Ko-Wei Lin; Kai Yu Jen; Carlos Jose Suarez; Erika C Crouch; David L Perkins; Patricia W Finn Journal: J Immunol Date: 2010-04-30 Impact factor: 5.422
Authors: Sangita P Patil; Juan P Wisnivesky; Paula J Busse; Ethan A Halm; Xiu-Min Li Journal: Ann Allergy Asthma Immunol Date: 2011-01-14 Impact factor: 6.347
Authors: Jason P Lynch; Rhiannon B Werder; Bodie F Curren; Md Al Amin Sikder; Ashik Ullah; Ismail Sebina; Ridwan B Rashid; Vivian Zhang; John W Upham; Geoff R Hill; Raymond J Steptoe; Simon Phipps Journal: Mucosal Immunol Date: 2020-02-17 Impact factor: 7.313