Gamma delta T cells kill myeloma cells by sensing mevalonate metabolites and ICAM-1 molecules on cell surface.
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.
Uchida
Ryo
R
Division of Hematology and Oncology, Department of Medicine, Kyoto Prefectural University of Medicine, Kyoto, Japan.
Ashihara
Eishi
E
Sato
Kiyoshi
K
Kimura
Shinya
S
Kuroda
Junya
J
Takeuchi
Miki
M
Kawata
Eri
E
Taniguchi
Kyoko
K
Okamoto
Masashi
M
Shimura
Kazuho
K
Kiyono
Yasushi
Y
Shimazaki
Chihiro
C
Taniwaki
Masafumi
M
Maekawa
Taira
T
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
D008565:Membrane Proteins; D016692:Receptors, Antigen, T-Cell, gamma-delta; D018799:Intercellular Adhesion Molecule-1; D008798:Mevalonic Acid