Suppression of IgE antibody responses by NKT cells-mechanisms of NKT cell-mediated regulatory function

Vα14 natural killer T (NKT) cells exhibit various immune-regulatory properties in vivo. A repeated injection of α-galactosylceramide (α-GalCer) into mice induced suppression of antigen-specific IgE, IgG1 and IgG2a production in vivo. The suppression of antigen specific Ig responses seems to be due to the generation of regulatory DCs producing high IL-10 and low IL-12 by IL-10 derived from Vα14 NKT cells, because repeated α-GalCer stimulation changed cytokine profiles, such as high IL-10 and low IFN-γ production in Vα14 NKT cells. The unique cytokine profile (high IL-10 and low IL-12) in the regulatory DCs appeared to be regulated by upregulation of phosphorylation of extracellular signal-regulated kinase-1/2 and augmented production of IκB_NS. The regulatory DCs thus induced in turn generated antigen specific Tr1 type regulatory T cells producing IL-10 suppressing Ig responses in an antigen specific fashion.