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

• DOI: 10.1067/mai.2002.127512
• Publication Date: 2002-10-09T21:24:11Z
• Authors: Jae-Won Oh; Christine M. Seroogy; Everett H. Meyer; Omid Akbari; Gerald Berry; C.Garrison Fathman; Rosemarie H. DeKr...; Dale T. Umetsu
• Keywords: Inflammation; Mice, Inbred BALB C; Dose-Response Relationship, Drug; Ovalbumin; Genetic Therapy; Mice, SCID; T-Lymphocytes, Helper-Inducer; Allergens; Protein Engineering; Asthma; Cell Line; Interleukin-10; 3. Good health; Mice; 03 medical and health sciences; Th2 Cells; 0302 clinical medicine; Transduction, Genetic; Animals; Cytokines; Bronchial Hyperreactivity; Pulmonary Eosinophilia; Methacholine Chloride

T(H)2 cells play a critical role in the pathogenesis of asthma, but the precise immunologic mechanisms that inhibit T(H)2 cell function in vivo are not well understood.The purpose of our studies was to determine whether T cells producing IL-10 regulate the development of asthma.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.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 T(H)2 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.Our results demonstrate that T cells secreting IL-10 in the respiratory mucosa can indeed regulate T(H)2-induced airway hyperreactivity and inflammation, and they strongly suggest that IL-10 plays an important inhibitory role in allergic asthma.