Asp f I CD4+ TH2-like T-cell lines in allergic bronchopulmonary aspergillosis

Abstract

Allergic bronchopulmonary aspergillosis (ABPA) is a hypersensitivity lung disease caused by bronchial colonization with Aspergillus fumigatus (Af) characterized by elevated serum total and Af-specific IgE levels and eosinophilia. In order to examine T-cell reactivity to Af antigens, six T-cell lines were established from the peripheral blood of patients with ABPA to Asp f I, an 18 kd protein purified from Af extracts. The Asp f I-specific T-cell lines, analyzed by flow cytometry, were 100% CD3+ CD4+. Lymphoproliferative responses of the T-cell lines were specific for Asp f I stimulation, 28,999 cpm (stimulation index = 12.2), and showed no response to tetanus toxoid stimulation, 2178 cpm (stimulation index = 1.1) (p < 0.001). Furthermore, Asp f I-stimulated lymphoproliferation was inhibited in two experiments by monoclonal anti-interleukin (IL)-4 antibody in a dose-response fashion, 78% and 84% inhibition at 5% concentration of anti-IL-4. In contrast, anti-IL-2 antibody did not inhibit Asp f I-stimulated proliferation. Asp f I-stimulated T-cell lines synthesized predominantly IL-4 (mean, 21.5 ng/ml) after 48 hours of culture, and nondetectable quantities of interferon-gamma and IL-2. In summary, Asp f I-specific T-cell lines established from patients with ABPA were characterized as being CD4+ TH2-like in their cytokine synthesis pattern, and secreted IL-4 behaved in an autocrine fashion, stimulating proliferation.