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

Abstract

Background: TH2 cells play a critical role in the pathogenesis of asthma, but the precise immunologic mechanisms that inhibit TH2 cell function in vivo are not well understood. Objective: The purpose of our studies was to determine whether T cells producing IL-10 regulate the development of asthma. Methods: We used gene therapy to generate ovalbumin-specific CD4 T-helper cells to express IL-10, and we examined their capacity to regulate allergen-induced airway hyperreactivity. Results: We demonstrated that the CD4 T-helper cells engineered to express IL-10 abolished airway hyperreactivity and airway eosinophilia in BALB/c mice sensitized and challenged with ovalbumin and in SCID mice reconstituted with ovalbumin-specific TH2 effector cells. The inhibitory effect of the IL-10-secreting T-helper cells was accompanied by the presence of increased quantities of IL-10 in the bronchoalveolar lavage fluid, was antigen-specific, and was reversed by neutralization of IL-10. Moreover, neutralization of IL-10 by administration of anti-IL-10 mAb in mice sensitized and challenged with ovalbumin seriously exacerbated airway hyperreactivity and airway inflammation. Conclusion: Our results demonstrate that T cells secreting IL-10 in the respiratory mucosa can indeed regulate TH2-induced airway hyperreactivity and inflammation, and they strongly suggest that IL-10 plays an important inhibitory role in allergic asthma.