CD4+ T helper cells engineered to produce IL-10 reverse allergen-induced airway hyperreactivity and inflammation

초록

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. Using gene therapy, we demonstrated that ovalbumin-specific (OVA-specific) Th cells engineered to express IL-10 abolished airway hyperreactivity and airway inflammation induced by OVA-specific Th2 effector cells in SCID and BALB/c mice. These effects are dose dependent, correlated with increased concentrations of active IL-10 in the bronchoalveolar lavage (BAL) fluid, demonstrating that latent IL-10 was activated in the inflammatory environment. The inhibitory effect of IL-10 producing CD4+ cells was antigen-specific and was reversed by neutralization of IL-10. Our results demonstrate that IL-10 transduced CD4 T cells in the respiratory mucosa can indeed regulate Th2-induced airway hyperreactivity and inflammation.