The effects of αGalCer-induced TCRVα24 Vβ11+ natural killer T cells on NK cell cytotoxicity in umbilical cord blood
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- Ueda, Y., Hagihara, M., Gansuvd, B. et al. Cancer Immunol Immunother (2003) 52: 625. doi:10.1007/s00262-003-0398-3
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The first objective of this study was to investigate in vitro effects of α-galactosylceramide (αGalCer) on the proliferation of umbilical cord blood (UCB) natural killer T (NKT) cells and enhancement of their cytotoxicity. The second one is to examine whether purified NKT cells could affect the cytotoxicity of UCB-NK cells either in the presence or absence of dendritic cells (DCs).
Mononuclear cells (MNCs) from UCB were cultured for 2 weeks in the presence of IL-2 (100 U/ml), with or without αGalCer. The effect of neutralizing monoclonal antibodies (MoAb) against TCRVα24 and CD1d was also examined. TCRVα24 Vβ11 double positive NKT cells were purified by FACS sorter and then cocultured with syngeneic isolated UCB−CD56+NK cells in either the presence or absence of DCs. The cytotoxicity against various malignant cell targets and cytokine production was determined.
The addition of αGalCer induced human NKT cells to proliferate in UCB-MNCs to a greater extent than in adult PB-MNCs. However, it suppressed the cytotoxic activity against malignant cell targets. Anti-TCRVα24 and CD1d MoAb recovered the cytotoxicity by inhibiting the proliferation of UCB-NKT cells. NKT cells cocultured with auto-DCs significantly increased NK cell cytotoxicity against K562, and Raji cells and produced IFN-γ at much higher levels than UCB-NKT cells alone.
In UCB samples, αGalCer–pulsed DCs and NKT cells acted together to enhance NK cytotoxicity in vitro.