title: Gamma delta T cells kill myeloma cells by sensing mevalonate metabolites and ICAM-1 molecules on cell surface.
abstract: We evaluated the mechanism of recognition of myeloma cells by gammadeltaT cells. The expanded gammadeltaT cells killed RPMI8226 and U266 myeloma cells in a gammadeltaT-cell dose-dependent manner. Pretreatment of myeloma cells with zoledronic acid or mevastatin showed that gammadeltaT cells kill myeloma cells by recognizing the mevalonate metabolites. The expression level of intercellular cell adhesion molecule-1 (ICAM-1) on myeloma cells correlates with the cytotoxicity by gammadeltaT cells. Pretreatment of RPMI8226 and U266 with an anti-ICAM-1 monoclonal antibody inhibited their cytolysis. Moreover, AMO-1 myeloma cells transfected with of human ICAM-1 cDNA were susceptible to gammadeltaT cells compared to parental AMO-1 cells. In conclusion, gammadeltaT cells recognize the mevalonate metabolites and ICAM-1 on myeloma cells.
authors.affiliation: Division of Hematology and Oncology, Department of Medicine, Kyoto Prefectural University of Medicine, Kyoto, Japan.
authors.forename: Ryo
authors.initials: R
authors.lastname: Uchida
authors.forename: Eishi
authors.initials: E
authors.lastname: Ashihara
authors.forename: Kiyoshi
authors.initials: K
authors.lastname: Sato
authors.forename: Shinya
authors.initials: S
authors.lastname: Kimura
authors.forename: Junya
authors.initials: J
authors.lastname: Kuroda
authors.forename: Miki
authors.initials: M
authors.lastname: Takeuchi
authors.forename: Eri
authors.initials: E
authors.lastname: Kawata
authors.forename: Kyoko
authors.initials: K
authors.lastname: Taniguchi
authors.forename: Masashi
authors.initials: M
authors.lastname: Okamoto
authors.forename: Kazuho
authors.initials: K
authors.lastname: Shimura
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Kiyono
authors.forename: Chihiro
authors.initials: C
authors.lastname: Shimazaki
authors.forename: Masafumi
authors.initials: M
authors.lastname: Taniwaki
authors.forename: Taira
authors.initials: T
authors.lastname: Maekawa
mesh_terms: D045744:Cell Line, Tumor; D002462:Cell Membrane / Q000378:metabolism; D003602:Cytotoxicity, Immunologic; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism*; D008565:Membrane Proteins / Q000378:metabolism*; D008798:Mevalonic Acid / Q000378:metabolism*; D009101:Multiple Myeloma / Q000276:immunology* / Q000378:metabolism; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000502:physiology*; D013601:T-Lymphocytes / Q000276:immunology* / Q000378:metabolism
chemical_list: D008565:Membrane Proteins; D016692:Receptors, Antigen, T-Cell, gamma-delta; D018799:Intercellular Adhesion Molecule-1; D008798:Mevalonic Acid