CD54/ICAM-1 is a costimulator of NK cell-mediated cytotoxicity

Cell Immunol. 1994 Aug;157(1):92-105. doi: 10.1006/cimm.1994.1208.

Abstract

The receptors and the array of cell adhesion molecules regulating MHC-unrestricted cytotoxic activity of NK cells toward tumor targets have not completely characterized. Antibody inhibition studies suggest roles for a number of cell adhesion molecules (CAMs). Recent studies suggest that CAMs can function to stabilize cell-to-cell interactions and/or to provide costimulatory signals that are crucial for T cell activation. It has been difficult to experimentally demonstrate that adhesion molecules also function as costimulators in NK cell-mediated cytotoxicity. We have developed an experimental system using cells transfected with genes encoding huICAM-1 and/or LFA-3 to investigate the function of adhesion molecules. Here we report that neither the expression of transfected ICAM-1 or LFA-3 alone nor the expression of both ICAM-1 and LFA-3, in the absence of MHC class I molecules, converts a murine cell line that is resistant to NK cell-mediated lysis into a susceptible one. We next tested the ability of ICAM-1 or LFA-3-mediated interactions to provide costimulation of NK cell cytolytic activity using a "three cell" experimental system comprising human NK cells, 51C-labeled target cells, and transfected mouse cells as a source of costimulation. The ability of NK cells to lyse K562 cells or anti-CD16-coated target cells was significantly enhanced by the addition of ICAM-1-transfected cells, whereas the addition of cells transfected with LFA-3 or irrelevant genes did not enhance lytic activity. Since the transfected huICAM-1 interacts with NK cells at sites spatially separate from the NK cell-target cell interactions, our data suggest that LFA-1-ICAM-1 or MAC-1-ICAM-1 interactions can provide remote costimulation, via signaling events, to induce cytotoxic activity in NK cells.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Antibodies, Monoclonal
  • Antigens, CD / physiology
  • Antigens, Differentiation, T-Lymphocyte / physiology
  • CD2 Antigens
  • CD58 Antigens
  • Cell Adhesion Molecules / physiology*
  • Cytotoxicity, Immunologic / physiology*
  • Flow Cytometry
  • Humans
  • Intercellular Adhesion Molecule-1
  • Killer Cells, Natural / physiology*
  • Lymphocyte Function-Associated Antigen-1 / physiology
  • Macrophage-1 Antigen / physiology
  • Major Histocompatibility Complex / physiology*
  • Membrane Glycoproteins / physiology
  • Receptors, Immunologic / physiology
  • Transfection
  • Tumor Cells, Cultured / immunology

Substances

  • Antibodies, Monoclonal
  • Antigens, CD
  • Antigens, Differentiation, T-Lymphocyte
  • CD2 Antigens
  • CD58 Antigens
  • Cell Adhesion Molecules
  • Lymphocyte Function-Associated Antigen-1
  • Macrophage-1 Antigen
  • Membrane Glycoproteins
  • Receptors, Immunologic
  • Intercellular Adhesion Molecule-1