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.