Valpha24+ natural killer T-cell responses against T-acute lymphoblastic leukaemia cells: implications for immunotherapy

Br J Haematol. 2003 Jul;122(2):231-9. doi: 10.1046/j.1365-2141.2003.04429.x.

Abstract

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.

MeSH terms

  • Antigens, CD1 / analysis
  • Cytokines / immunology
  • Cytotoxicity Tests, Immunologic
  • Humans
  • Immunophenotyping
  • Immunotherapy, Adoptive / methods*
  • Killer Cells, Natural / immunology*
  • Leukemia-Lymphoma, Adult T-Cell / immunology*
  • Lymphocyte Activation
  • Receptors, Antigen, T-Cell, alpha-beta / immunology*
  • Tumor Cells, Cultured

Substances

  • Antigens, CD1
  • Cytokines
  • Receptors, Antigen, T-Cell, alpha-beta