Role of alpha-galactosylceramide-activated Valpha14 natural killer T cells in the regulation of allergic diseases

Abstract

Valpha14 natural killer T (NKT) cells produce large amounts of both IL-4 and IFN-gamma upon stimulation with a ligand, alpha-galactosylceramide (alpha-GalCer), and play a crucial role in various immune responses, including allergic reactions. Interestingly, Valpha14 NKT cells are not essential for the induction of specific IgE response but they instead tend to induce suppression of specific IgE upon alpha-GalCer activation in vivo. The suppression in the IgE production is not detected either in Valpha14 NKT cell-deficient mice or in IFN-gamma-deficient mice. Therefore, activated Valpha14 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-gamma. In an OVA-induced asthma model, alpha-GalCer administration inhibited airway inflammation and airway hyperreactivity by IFN-gamma from activated Valpha14 NKT cells, thus suggesting the negative regulation of Th2-responses by the activated Valpha14 NKT cells.