T cell cytokine synthesis in cystic fibrosis patients with allergic bronchopulmonary aspergillosis

Abstract

Rationale ABPA is characterized by a heightened Th2 response to A. fumigatus allergens compared to patients without ABPA. We hypothesize that one reason for this response is skewed Th2 T-cell responses in patients with ABPA. Methods PBLs were stimulated non-specifically with PMA/ionomycin for 2 days and with antigens tetanus toxoid and Asp f2, f3 and f4 from 1 to 7 days. Culture supernatants were examined for cytokine synthesis. Results Following PMA/IO stimulation, IFN-, TNF-, and IL-2 synthesis were increased comparably in ABPA and non-ABPA patients; synthesis of IL-4, IL-5 and IL-10 were low in both ABPA and non-ABPA patients. Following tetanus toxoid and Asp f2/f3/f4 stimulations, ABPA and non-ABPA patients had decreased IFN- synthesis compared to normal controls. Following Asp f2/f3/f4 stimulation and Asp f2, f3, f4 individually, ABPA patients had increased IL-5 synthesis compared to non-ABPA patients. Increased IL-10 synthesis was seen in ABPA and non-ABPA patients following Asp f2/f3/f4 stimulation; however, TGF- synthesis was not increased. When the kinetics of IL-10 synthesis were examined, IL-10 synthesis was increased on Day 1; IL-5 synthesis was detected on Day 3 and increased on Days 5 and 7 in ABPA patients; IFN- synthesis was detected on Day 3and increased on Days 5 and 7 in both ABPA and non-ABPA patients. Conclusions ABPA patients have increased Th2 cytokine pattern in Asp f2, f2 and f4 stimulated cultures. Aspergillus allergens induced IL-10 synthesis in both ABPA and non-ABPA CF patients, skewing a Th2 response to A. fumigatus colonization in ABPA patients.