Vα24+ natural killer T-cell responses against T-acute lymphoblastic leukaemia cells:: implications for immunotherapy

Human Valpha24(+) natural killer T (NKT) cells correspond to mouse Valpha14(+) NKT cells, both cell types use an invariant T-cell receptor-alpha chain and are activated by glycolipids in a CD1d-dependent manner. Mouse Valpha14(+) NKT cells have been reported to have an antitumour effect in vivo. Human Valpha24(+) NKT cells can kill a proportion of tumour cells in a CD1d-dependent manner in vitro. We report here that many human leukaemic T-cell lines express CD1d and can be directly killed by Valpha24(+) NKT cells. This killing activity was enhanced in the presence of alpha-galactosylceramide (alpha-GalCer), a ligand of Valpha24(+) NKT cells. Moreover, primary leukaemic T cells from five of eight T-cell acute lymphoblastic leukaemia (T-ALL) patients expressed CD1d and were good targets of Valpha24(+) NKT cells. This cytotoxicity was increased in the presence of alpha-GalCer. Our results suggest that T-ALL is a good candidate for Valpha24(+) NKT-cell-based immuno-cell therapy.