[Immunopathogenesis of allergic bronchial asthma. Detection of activated CD25-CD4 lymphocytes and release of cytokines in the bronchoalveolar space following segmental allergen challenge].
The aim of this study was to investigate the fundamental processes underlying the inflammatory response to allergen in mild non-symptomatic asthmatics, using a new model entailing endobronchial segmental provocation. Ten asymptomatic asthmatic volunteers (8 male, 2 female; mean age 28.2 [24-41] years) were challenged employing the segmental allergen provocation technique. 250 PNU in 5 ml 0.9% NaCl solution of either birch (n = 8) or grass (n = 2) pollen were instilled into one segment. As control, only the solvent was instilled into a segment of the contralateral lung. Bronchoalveolar lavage (BAL) with 100 ml prewarmed saline was performed 10 min and 18 h after allergen provocation. The cellular distribution and activation state in BAL fluid and peripheral blood was analysed by immunofluorescence and flow cytometry. The concentration of various cytokines was determined in the BAL fluid using ELISA and bioassays. In blood, segmental allergen provocation led to an increase both in numbers of neutrophils (3833 cells/microliters vs 6830 cells/microliters; P < 0.005) and activated IL-2R expressing (CD25+) CD4+ T cells (3.6% vs 4.8% of all CD4+ lymphocytes; P < 0.05). No change was observed in eosinophils and other leukocytes and lymphocyte subsets. In contrast, a significant 30-fold increase in eosinophils (0.39 x 10(6) vs 11.5 x 10(6) cells/100 ml; P < 0.01) and a twofold increase in CD25+ CD4+ T cells (P < 0.05) were found in BAL samples 18 h after segmental allergen challenge, when compared to the control segment. Analysis of the cytokine profile revealed significantly increased levels of several cytokines. Allergen challenge of extrinsic asthmatic subjects causes differentiation of activated CD25+ CD4+ lymphocytes which may contribute to the pathogenesis of the asthmatic inflammation through the release of various cytokines.
Kroegel
C
C
Abteilung Pneumologie, Medizinische Klinik der Universität Freiburg.
Häfner
D
D
Walker
C
C
Luttmann
W
W
Matthys
H
H
Virchow
J C
JC
D000328:Adult; D000485:Allergens / Q000276:immunology; D001249:Asthma / Q000276:immunology*; D001681:Biological Assay; D001985:Bronchial Provocation Tests; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D016207:Cytokines / Q000378:metabolism*; D004797:Enzyme-Linked Immunosorbent Assay; D004804:Eosinophils / Q000276:immunology; D005260:Female; D005434:Flow Cytometry; D005455:Fluorescent Antibody Technique; D006801:Humans; D007958:Leukocyte Count; D016131:Lymphocyte Subsets / Q000276:immunology; D008297:Male; D009504:Neutrophils / Q000276:immunology; D011058:Pollen / Q000276:immunology; D015375:Receptors, Interleukin-2 / Q000032:analysis*; D013997:Time Factors
D000485:Allergens; D016207:Cytokines; D015375:Receptors, Interleukin-2
Immunpathogenese des allergischen Asthma bronchiale. Nachweis aktivierter CD25-CD4-Lymphozyten und Freisetzung von Zytokinen im Bronchoalveolarraum nach segmentaler Allergenprovokation.