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

Abstract

Human Vα24+ natural killer T (NKT) cells correspond to mouse Vα14+ NKT cells, both cell types use an invariant T-cell receptor-α chain and are activated by glycolipids in a CD1d-dependent manner. Mouse Vα14+ NKT cells have been reported to have an antitumour effect in vivo. Human Vα24+ 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 Vα24+ NKT cells. This killing activity was enhanced in the presence of α-galactosylceramide (α-GalCer), a ligand of Vα24+ 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 Vα24+ NKT cells. This cytotoxicity was increased in the presence of α-GalCer. Our results suggest that T-ALL is a good candidate for Vα24+ NKT-cell-based immuno-cell therapy.