CD4+ T Helper Cells Engineered to Produce IL-10 Reverse Allergen-induced Airway Hyperreactivity and Inflammation / 소아알레르기및호흡기학회지

ABSTRACT

PURPOSE: Asthma is characterized by airway hyperreactivity to a variety of specific and nonspecific stimuli, by chronic airway inflammation with pulmonary eosinophilia, by mucus hypersecretion, and by increased serum IgE levels. T helper 2 (Th2) cells play a critical role in the pathogenesis of asthma, but the precise immunological mechanism that inhibit Th2 cell function in vivo are not well understood. METHODS: Using gene therapy, Th-cell lines were transferred intravenously into histocompatible SCID or OVA immunized BALB/c mice. Airway responsiveness was assessed by methacholine-induced airflow obstruction from conscious mice placed in a whole-body plethysmograph. Pulmonary airflow obstruction was measured by enhanced pause (Penh). RESULTS: We demonstrated that ovalbumin-specific (OVA-specific) Th cells engineered to express IL-10 abolished airway hyperreactivity induced by OVA-specific Th2 effector cells in SCID and BALB/c mice. The inhibitory effect of IL-10 transduced Th cells was antigen-specific and was reversed by neutralization of IL-10. CONCLUSION: Our results demonstrate that IL-10 transduced CD4+ Th cells in the respiratory mucosa can indeed regulate Th2-induced airway hyperreactivity.