Role of α-Galactosylceramide-activated Vα14 Natural Killer T Cells in the Regulation of Allergic Diseases

ABSTRACTVα14 natural killer T (NKT) cells produce large amounts of both IL-4 and IFN-γ upon stimulation with a ligend, α-galactosylceramide (α-GalCer), and play a crucial role in various immune responses, including allergic reactions. Interestingly, Vα14 NKT cells are not essential for the induction of specific IgE response but they instead tend to induce suppression of specific IgE upon α-GalCer activation in vivo. The suppression in the IgE production is not detected either in Va14 NKT cell-deficient mice or in IFN-γ-deficient mice. Therefore, activated Vα14 NKT cells are able to exert a potent suppressive activity on Th2 cell differentiation and subsequent IgE production by producing a large amount of IFN-γ. In an OVA-induced asthma model, α-GalCer administration inhibited airway inflammation and airway hyperreactivity by IFN-γ from activated Vα14 NKT cells, thus suggesting the negative regulation of Th2-responses by the activated Vα14 NKT cells.