IL-15 prevents allergic rhinitis through reactivation of antigen-specific CD8+ cells

Background: Allergic rhinitis is one of the most common allergic inflammatory diseases characterized by a predominant T(H)2 response with antigen-specific IgE synthesis. IL-15 plays important roles in activation and maintenance of memory CD8(+)T cells capable of producing IFN-gamma, which regulates TH2 responses. Objective: To investigate the roles of endogenous IL-15 in allergic inflammation, we examined allergic rhinitis in IL-15 knockout (KO) mice sensitized with ovalbumin followed by intranasal rechallenge with ovalbumin. Methods: IL-15KO mice were sensitized intraperitoneaily with oval bumin/complete Freund's adjuvant on day 0 and ovalbumin/1FA on day 7, and then were intranasally challenged with ovalbumin on days 21, 22, 23, 24, and 25. Nasal symptoms and histologic changes were examined. IgE production and T(H)2 responses were measured by ELISA. Purified CD8+T cells or recombinant IL-15 were administered into ovalbumin-sensitized mice. Results: The levels of IgE production and TH2 responses in IL-15KO mice were comparable to those in control mice a er ovalbumin sensitization. However, sneezing, infiltration of eosinophils into the nasal mucosa, and TH2 cytokine production were aggravated in ovalbumin-sensitized IL-15KO mice after intranasal challenge with ovalbumin. Adoptive transfer of CD8(+) T cells from ovalbumin-sensitized mice suppressed the T(H)2 responses in mice but not in IL-15KO mice. Administration of IL-15 with oval bumin significantly prevented the development of allergic rhinitis in ovalbumin-sensitized mice. Conclusion: We demonstrate with IL-15KO mice that endogenous IL-15 plays an important role in suppression of allergic rhinitis at effector phase. Intranasal administration of IL-15 is useful as a therapeutic approach to control allergic rhinitis. Clinical implications: Intranasal administration of recombinant IL-15 might become new immunotherapy for allergic rhinitis.