Allergen-induced proliferation and interleukin-5 production by bronchoalveolar lavage and blood T cells after segmental allergen challenge.
In order to detect and characterize allergen-specific T cells in the airways of atopic asthmatics, we measured proliferation and cytokine production by bronchoalveolar lavage (BAL) T cells isolated from Dermatophagoides pteronyssinus (Der p)-sensitive asthmatics and nonatopic control subjects, and compared the results with those generated using peripheral blood (PB) T cells. BAL and PB mononuclear cells were collected 24 h after segmental allergen challenge by fibreoptic bronchoscopy and venepuncture, respectively. T cells purified from BAL and PB were stimulated with autologous, irradiated antigen-presenting cells and D. pteronyssinus extract or a control, nonallergen antigen (M. tuberculosis purified protein derivative [PPD]). IL-5 and IFN-gamma concentrations were measured in culture supernatants by ELISA, and T-cell proliferation by 3H-thymidine uptake. D. pteronyssinus-induced proliferation of T cells derived from both BAL and PB was elevated in asthmatics when compared with control subjects (p < 0.05), whereas PPD-induced proliferation was equivalent in both compartments. In the asthmatics, D. pteronyssinus-induced proliferative responses of equivalent numbers of BAL and PB T cells obtained after allergen challenge were statistically equivalent. Nevertheless, BAL T cells stimulated with D. pteronyssinus produced significantly greater amounts of IL-5 than did PB T cells (p < 0.05). Allergen-induced proliferation and IL-5 production by BAL T cells in the asthmatics after segmental allergen challenge correlated with the percentages of eosinophils in the BAL fluid (p < 0.01). Further, BAL T cells from asthmatic patients produced significantly higher amounts of IL-5 than did the same number of cells from nonatopic control subjects (p < 0.05). We conclude that, in D. pteronyssinus-sensitive asthmatics, allergen-specific T cells can be detected in the bronchial lumen after allergen challenge and that allergen-induced proliferation and IL-5 production by these cells correlates with local eosinophil influx. Although bronchial luminal T cells show an equivalent proliferative response to allergen stimulation as compared with PB T cells, they do produce more IL-5, consistent with the hypothesis that local differentiation or priming of these cells within the bronchial mucosal environment results in upregulation of allergen-induced IL-5 secretion.
Imperial College School of Medicine, National Heart and Lung Institute, Charing Cross and Royal Brompton Campuses, London, United Kingdom.
S J
SJ
Till
S R
SR
Durham
K
K
Rajakulasingam
M
M
Humbert
D
D
Huston
R
R
Dickason
A B
AB
Kay
C J
CJ
Corrigan
D000328:Adult; D001249:Asthma / Q000276:immunology*; D001985:Bronchial Provocation Tests; D001992:Bronchoalveolar Lavage Fluid; D002455:Cell Division; D005260:Female; D006098:Granulocytes / Q000276:immunology; D006801:Humans; D066298:In Vitro Techniques; D007249:Inflammation / Q000276:immunology; D007371:Interferon-gamma; D015848:Interleukin-5 / Q000096:biosynthesis*; D007963:Leukocytes, Mononuclear / Q000276:immunology*; D008297:Male; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology*
D015848:Interleukin-5; D007371:Interferon-gamma