IMMUNOPATHOGENESIS OF BRONCHIAL-ASTHMA - DIFFERENTIATION OF ACTIVATEDCD25(+) CD4(+) LYMPHOCYTES AND RELEASE OF CYTOKINES INTO THE BRONCHOALVEOLAR SPACE FOLLOWING SEGMENTAL ALLERGEN CHALLENGE

The aim of this study was to investigate the fundamental processes und erlying the inflammatory response to allergen in mild non-symptomatic asthmatics, using a new model entailing endobronchial segmental provoc ation. The asymptomatic asthmatic volunteers (8 male, 2 female; mean a ge 28.2 [24-41] years) were challenged employing the segmental allerge n 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 contrala teral 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 w as analysed by immunofluorescence and flow cytometry. The concentratio n of various cytokines was determined in the BAL fluid using ELISA and bioassays. In blood, segmental allergen provocation led to an increas e both in numbers of neutrophils (3833 cells/mu l vs 6830 cells/mu l; 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 observe d in eosinophils and other leukocytes and lymphocyte subsets. In contr ast, 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(+) C D4(+) T cells (P < 0.05) were found in BAL samples 18 h after segmenta l allergen challenge, when compared to the control segment. Analysis o f the cytokine profile revealed significantly increased levels of seve ral cytokines. - Allergen challenge of extrinsic asthmatic subjects ca uses differentiation of activated CD25(+) CD4(+) lymphocytes which may contribute to the pathogenesis of the asthmatic inflammation through the release of various cytokines.