Increased antigen-specific Th-2 response in allergic bronchopulmonary aspergillosis (ABPA) in patients with cystic fibrosis

Abstract

The majority of patients with cystic fibrosis (CF) become colonized with Aspergillus fumigatus (A. fumigatus) in the lower respiratory tract, the prevalence being up to 60%. Between 1-11% of CF patients develop allergic bronchopulmonary aspergillosis (ABPA). Previous studies of ABPA in selected patients suffering from cystic fibrosis or atopic asthma have suggested a pathogenic role for antigen-specific "Th2-like" T lymphocytes. The aim of this study was to evaluate the quantitative importance of such Th2 cells, using improved techniques for measuring interleukin-4 (IL-4) and IL-5 secretion in unseparated peripheral blood mononuclear cell (PBMC) suspensions from CF patients with ABPA and from a control group without ABPA. Thus, 20 patients with CF, heavily colonized with A. fumigatus in the lower respiratory tract, were studied: 10 patients with ABPA, and 10 without. Unseparated PBMC were stimulated in vitro by A. fumigatus antigen and by an unrelated antigen (tetanus toxoid) as a control. After 6 days of stimulation, IL-4 and IL-5 (markers for Th2 cell activity) and interferon-gamma (IFN-gamma) (marker for Th1 cell activity) were quantified in the supernatants by enzyme-linked immunosorbent assay. PBMC from ABPA patients secreted significantly higher amounts of IL-4, i.e., 0.48 (0.15-0.8) ng/mL (median (range)), and IL-5, 37.64 (0.32-82.85) ng/mL, compared to secretions obtained in non-ABPA CF controls of 0.07 (0.04-0.16) ng/mL and 3.00 (0.10-5.09) ng/mL, respectively (P < 0.01 for both). IFN-gamma secretion was similar in the two groups, amounting to 21.5 (2.05-72.5) ng/mL in ABPA patients vs. 20.75 (1.80-54.0) ng/mL in non-ABPA patients (P = 0.47). No significant differences were obtained in the cytokine secretion induced by tetanus toxoid stimulation between the two groups. We conclude that ABPA in CF patients is associated with an antigen-specific, Th2-like T-cell immune response, as indicated by excessive secretion of IL-4 and IL-5.