Development of New Immunotherapy for Oral Cancer Using Dendritic Cells

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Natural killer T (NKT) cells produce large amounts of cytokines associated with both the Th1 response (IFN-γ) and Th2 response (IL-4) after being stimulated by the synthetic CD1d ligand α-galactosylceramide (α-GalCer) by their invariant Vα14 receptor. However, the role played by adhesion or co-stimulation molecules in the activation of NKT cells by α-GalCer remains unclear. To address this issue, LFA-1^+ and CD28^+ mice were used to investigate IL-4 and IFN-γ production by NKT cells following α-GalCer stimulation. LFA-1^+ mice showed increased IL-4 production in response to in vitro and in vivo polarized Th2-type responses, represented by activation of B cells and serum IgE elevation. In contrast, impairment of production of IL-4 and IFN-γ in CD28^+ mice resulted in a profound inability to polarize the Th2-type response, represented by the abolishment of serum IgE. These results imply that the LFA-1 adhesion receptor and the CD28 co-stimulatory receptor selectively regulate Th1- and Th2-like functions of α-GalCer-activated NKT cells.