Gamma delta T cells kill myeloma cells by sensing mevalonate metabolites and ICAM-1 molecules on cell surface

Biochem Biophys Res Commun. 2007 Mar 9;354(2):613-8. doi: 10.1016/j.bbrc.2007.01.031. Epub 2007 Jan 16.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Line, Tumor
  • Cell Membrane / metabolism
  • Cytotoxicity, Immunologic*
  • Humans
  • Intercellular Adhesion Molecule-1 / metabolism*
  • Membrane Proteins / metabolism*
  • Mevalonic Acid / metabolism*
  • Multiple Myeloma / immunology*
  • Multiple Myeloma / metabolism
  • Receptors, Antigen, T-Cell, gamma-delta / physiology*
  • T-Lymphocytes / immunology*
  • T-Lymphocytes / metabolism

Substances

  • Membrane Proteins
  • Receptors, Antigen, T-Cell, gamma-delta
  • Intercellular Adhesion Molecule-1
  • Mevalonic Acid