title: Natural killer-like nonspecific tumor cell lysis mediated by specific ligand-activated Valpha14 NKT cells.
abstract: We have recently identified alpha-galactosylceramide (alpha-GalCer) as a specific ligand for an invariant Valpha14/Vbeta8.2 T cell receptor exclusively expressed on the majority of Valpha14 NKT cells, a novel subset of lymphocytes. Here, we report that alpha-GalCer selectively activates Valpha14 NKT cells resulting in prevention of tumor metastasis. The effector mechanisms of the ligand-activated Valpha14 NKT cells seem to be mediated by natural killer (NK)-like nonspecific cytotoxicity. Indeed, the cytotoxic index obtained by alpha-GalCer-activated Valpha14 NKT cells was reduced by the addition of cold target tumor cells or by treatment with concanamycin A, which inhibits activation and secretion of perforin, but not by mAbs against molecules involved in the NKT cell recognition and conventional cytotoxicity, such as CD1d, Vbeta8, NK1. 1, Ly49C, Fas, or Fas ligand. These results suggest that the ligand-activated Valpha14 NKT cells kill tumor cells directly through a CD1d/Valpha14 T cell receptor-independent, NK-like mechanism.
authors.affiliation: Core Research for Evolutional Science and Technology Project, Japan Science and Technology Corporation and Division of Molecular Immunology, Center for Biomedical Science, School of Medicine, Chiba University, 1-8-1 Inohana, Chuo, Chiba 260-8670, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Kawano
authors.forename: J
authors.initials: J
authors.lastname: Cui
authors.forename: Y
authors.initials: Y
authors.lastname: Koezuka
authors.forename: I
authors.initials: I
authors.lastname: Toura
authors.forename: Y
authors.initials: Y
authors.lastname: Kaneko
authors.forename: H
authors.initials: H
authors.lastname: Sato
authors.forename: E
authors.initials: E
authors.lastname: Kondo
authors.forename: M
authors.initials: M
authors.lastname: Harada
authors.forename: H
authors.initials: H
authors.lastname: Koseki
authors.forename: T
authors.initials: T
authors.lastname: Nakayama
authors.forename: Y
authors.initials: Y
authors.lastname: Tanaka
authors.forename: M
authors.initials: M
authors.lastname: Taniguchi
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology; D003602:Cytotoxicity, Immunologic; D005699:Galactosylceramides / Q000378:metabolism*; D006801:Humans; D007694:Killer Cells, Natural / Q000276:immunology*; D008024:Ligands; D018942:Macrolides; D008546:Melanoma, Experimental / Q000276:immunology / Q000473:pathology; D008562:Membrane Glycoproteins / Q000378:metabolism; D051379:Mice; D054353:Perforin; D052899:Pore Forming Cytotoxic Proteins; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000378:metabolism*; D014407:Tumor Cells, Cultured
chemical_list: D000900:Anti-Bacterial Agents; D005699:Galactosylceramides; D008024:Ligands; D018942:Macrolides; D008562:Membrane Glycoproteins; D052899:Pore Forming Cytotoxic Proteins; D016693:Receptors, Antigen, T-Cell, alpha-beta; D054353:Perforin; C036978:concanamycin A