α-galactosylceramide-induced iNKT cells suppress experimental allergic asthma in sensitized mice: Role in IFN-γ

Abstract

Allergic asthma is a multifaceted syndrome consisting of eosinophil-rich airway inflammation, bronchospasm, and airway hyper-responsiveness (AHR). Using a mouse model of allergic asthma, we previously reported that invariant NKT (iNKT) cells increase the severity of this disease. Herein, we demonstrate that a single i.v. injection of α-galactosylceramide (α-GalCer), 1 h before the first airway allergen challenge of OVA-sensitized mice, abrogates elicitation of AHR, airway eosinophilia, IL-4 and IL-5 production in bronchoalveolar lavage fluid, and specific anti-OVA IgE antibodies. Further, α-GalCer administered intranasally also strongly inhibited the major symptoms of asthma in sensitized and challenged mice. α-GalCer treatment induces iNKT cell accumulation in the lungs, and shifts their cytokine profile from pro-asthmatic IL-4 to a protective IFN-γ production. The role of IFN-γ from iNKT cells in protection was shown by adoptive transfer of sorted iNKT cells from OVA-sensitized and α-GalCer-treated mice which protected immunized recipients from manifesting asthma by an IFN-γ-dependent pathway. Our findings demonstrate for the first time that α-GalCer administered locally inhibits asthma symptoms, even in predisposed asthmatic mice, through an iNKT cell and IFN-γ-dependent pathway. © 2005 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.