Valpha24+ 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.
Takahashi
Tsuyoshi
T
Department of Transfusion Medicine, Department of Haematology and Oncology, Faculty of Medicine, University of Tokyo, Japan.
Haraguchi
Kyoko
K
Chiba
Shigeru
S
Yasukawa
Masaki
M
Shibata
Yoichi
Y
Hirai
Hisamaru
H
D018949:Antigens, CD1 / Q000032:analysis; D016207:Cytokines / Q000276:immunology; D003601:Cytotoxicity Tests, Immunologic; D006801:Humans; D016130:Immunophenotyping; D016219:Immunotherapy, Adoptive / Q000379:methods*; D007694:Killer Cells, Natural / Q000276:immunology*; D015459:Leukemia-Lymphoma, Adult T-Cell / Q000276:immunology*; D008213:Lymphocyte Activation; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000276:immunology*; D014407:Tumor Cells, Cultured
D018949:Antigens, CD1; D016207:Cytokines; D016693:Receptors, Antigen, T-Cell, alpha-beta