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

• Published in: Journal of allergy and clinical immunology Vol. 110; no. 3; pp. 460 - 468
• Main Authors: Oh, Jae-Won, Seroogy, Christine M., Meyer, Everett H., Akbari, Omid, Berry, Gerald, Fathman, C.Garrison, DeKruyff, Rosemarie H., Umetsu, Dale T.
• Format: Journal Article
• Language: English
• Published: New York, NY Mosby, Inc 01.09.2002; Elsevier; Elsevier Limited
• Subjects: airway hyperreactivity; Allergens - immunology; Allergic diseases; Allergies; Animals; asthma; Asthma - immunology; Asthma - pathology; Asthma - therapy; Biological and medical sciences; Bronchial Hyperreactivity - immunology; Bronchial Hyperreactivity - prevention & control; Cell Line; Cytokines - biosynthesis; Disease; Dose-Response Relationship, Drug; Genetic Therapy; IL-10; Immunopathology; Inflammation - pathology; Inflammation - prevention & control; Interleukin-10 - antagonists & inhibitors; Interleukin-10 - genetics; Interleukin-10 - physiology; Laboratory animals; Lymphocytes; Medical sciences; Methacholine Chloride - pharmacology; Mice; Mice, Inbred BALB C; Mice, SCID; Ovalbumin - immunology; Protein Engineering; Pulmonary Eosinophilia - prevention & control; regulatory cells; Respiratory and ent allergic diseases; Studies; T-Lymphocytes, Helper-Inducer - immunology; T-Lymphocytes, Helper-Inducer - transplantation; TH2 cells; Th2 Cells - immunology; Transduction, Genetic; TH2 cells; airway hyperreactivity; TCR; YFP; KLH; asthma; Penh; AHR; OVA; BAL; IL-10; regulatory cells; Immunopathology; Allergy; Flow cytometry; Animal model; Hyperreactivity; Respiratory disease; Pathogenesis; Cytokine; Rodentia; Bronchus; Cell subpopulation; Asthma; Vertebrata; Regulation(control); Mammalia; Mouse; Animal; Interleukin 10; T-Lymphocyte; Th2 lymphocyte; Obstructive pulmonary disease
• ISSN: 0091-6749; 1097-6825
• DOI: 10.1067/mai.2002.127512

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. (J Allergy Clin Immunol 2002;110:460-8.)