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.
Mamessier
E
E
Université de Méditerranée, EA 3287, IFR125, France.
Nieves
A
A
Lorec
A-M
AM
Dupuy
P
P
Pinot
D
D
Pinet
C
C
Vervloet
D
D
Magnan
A
A
D000328:Adult; D000368:Aged; D001249:Asthma / Q000097:blood* / Q000503:physiopathology*; D005260:Female; D006801:Humans; D016753:Interleukin-10 / Q000097:blood; D018793:Interleukin-13 / Q000097:blood; D015847:Interleukin-4 / Q000097:blood; D015848:Interleukin-5 / Q000097:blood; D008297:Male; D008875:Middle Aged; D012720:Severity of Illness Index; D013601:T-Lymphocytes / Q000378:metabolism*; D050378:T-Lymphocytes, Regulatory / Q000378:metabolism
D018793:Interleukin-13; D015848:Interleukin-5; D016753:Interleukin-10; D015847:Interleukin-4