Allergen-induced Proliferation and Interleukin-5 Production by Bronchoalveolar Lavage and Blood T Cells after Segmental Allergen Challenge

Abstract

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.

T Cells from Human Allergen-Induced Late Asthmatic Responses Express IL-12 Receptor β2 Subunit mRNA and Respond to IL-12 In Vitro

“…We previously showed that under these conditions, allergeninduced IL-5 production is detectable in cultures of enriched BAL T cells from atopic asthmatics, but not peripheral blood T cells from the same patients, or BAL T cells from nonatopic normal subjects. Moreover, we reported that allergen-induced IL-5 production by BAL T cells correlated with allergen-induced eosinophilia in the bronchi (28).…”

“…We previously reported that IL-5 production by BAL, but not peripheral blood T cells stimulated with allergen and irradiated PBMC (as APC) correlates with the degree of airway eosinophilia and is higher in asthmatics than control subjects (28). Although the APC types in PBMC are unlikely to reflect the exact composition of APC in the lung, a previous report did not find differences in IL-12 responsiveness by allergen-specific peripheralblood T cells stimulated by different APC types (17).…”

“…ϩ memory T cells (32), show an increased tendency to undergo apoptosis (33), and, when collected 24 h aftersegmental allergen challenge, BAL T cells produce significantly greater amounts of IL-5 than equivalent numbers of freshly isolated peripheral blood T cells when stimulated with allergen in vitro (28).…”

Segmental Bronchial Provocation Induces Nasal Inflammation in Allergic Rhinitis Patients

“…A fiberoptic bronchoscope was introduced into the airway via the oral route, and mucosal biopsy specimens were taken from the carina of the left up-per and lower lobe. Subsequently, SBP was accomplished with a method described previously (16). The tip of the bronchoscope (BF, Type P20 D; Olympus Tokyo, Japan), was wedged in the anterior segment of the right upper lobe (RUL), and 10 ml of 0.9% sterile saline was instilled as a control challenge.…”

Autocrine interaction between IL-5 and IL-1β mediates altered responsiveness of atopic asthmatic sensitized airway smooth muscle

“…Additionally, IL-5 has been implicated in the development of airway constrictor hyperresponsiveness in various animal models of airway sensitization. Accordingly, recent studies have demonstrated that (a) treatment with IL-5 induces airway constrictor hyperresponsiveness (10)(11)(12); (b) certain strains of genetically IL-5-deficient mice fail to develop airway eosinophilia and constrictor hyperresponsiveness after allergen challenge in the sensitized state (35); and (c) transgenic mice that constitutively overexpress IL-5 exhibit airway inflammatory changes and constrictor hyperresponsiveness, both of which are pathognomonic of human allergic asthma (36). Notwithstanding this evidence, the mechanism(s) by which IL-5 reportedly elicits the proasthmatic phenotype of altered airway responsiveness remains to be identified.…”