[Repeated administration of alpha-galactosyl ceramide attenuates of natural killer T cells]

alpha-Galactosyl ceramide (alpha-GalCer) is well known as a specific ligand which can activate natural killer T (NKT) cells. This drug potentially induces anti-tumor effect of NKT cells, and clinical trials for alpha-GalCer in cancer patients are ongoing in the world. The aim of this study is to investigate how repeated alpha-GalCer injection affects the activation of NKT cells in mice. The initial administration of alpha-GalCer triggered a rapid production of both IFN-gamma and IL-4 in NKT cells and induced subsequent apoptosis in the majority of those cells. Meanwhile, no increase in IFN-gamma production was observed after further injections, and NKT cells maintained the low level secretion of IL-4 since the first injection. After repeated alpha-GalCer administration, activation markers on NKT cells were down-regulated and autologous cytotoxicity against liver cells decreased, suggesting that repeated stimulation attenuates the response of NKT cells to the ligand. These data indicate that prudent discussion is required to determine the dosing interval of alpha-GalCer in clinical applications. A further study is needed for establishing effective methods of sustained NKT cell activation.