Human cytomegalovirus UL18 alleviated human NK-mediated swine endothelial cell lysis

Biochem Biophys Res Commun. 2004 Feb 27;315(1):144-50. doi: 10.1016/j.bbrc.2004.01.027.

Abstract

Human cytomegalovirus UL18, a MHC class I homologue, is known to serve as a natural killer cell (NK) decoy and to ligate NK inhibitory receptors to prevent lysis of an infected target cell. To explore whether the cell surface expression of UL18 represents a potential immune suppressive approach to evade NK-mediated cytotoxicity in the prevention of xenograft rejection, we examined the effect of the UL18 expression in vitro upon human NK-mediated cytotoxicity against swine endothelial cells (SECs). UL18 expression on SECs by a retroviral vector (PLNCX2) significantly suppressed NK-mediated SEC lysis by approximately 25-100%. The protective effect of UL18 could be mediated through ILT-2 inhibitory receptor on NKs. Additionally, the interaction between UL18 and NKs resulted in the significant reduction of IFN-gamma production. This study demonstrates that UL18 can serve as an effective tool for the evasion of NK-mediated cytotoxicity and for the inhibition of IFN-gamma production during xenograft rejection.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antigens, CD / biosynthesis
  • Antigens, CD / immunology
  • Capsid Proteins / genetics
  • Capsid Proteins / immunology*
  • Capsid Proteins / metabolism
  • Cell Line
  • Cell Membrane / immunology
  • Cell Membrane / metabolism
  • Cytotoxicity, Immunologic
  • Endothelium, Vascular / cytology
  • Endothelium, Vascular / immunology*
  • Endothelium, Vascular / transplantation
  • Endothelium, Vascular / virology
  • Flow Cytometry
  • Fluorescent Antibody Technique, Indirect
  • HLA Antigens / biosynthesis
  • HLA Antigens / genetics
  • HLA Antigens / immunology
  • HLA-G Antigens
  • Histocompatibility Antigens Class I / biosynthesis
  • Histocompatibility Antigens Class I / genetics
  • Histocompatibility Antigens Class I / immunology
  • Humans
  • Interferon-gamma / metabolism
  • Killer Cells, Natural / immunology*
  • Leukocyte Immunoglobulin-like Receptor B1
  • Receptors, Immunologic / biosynthesis
  • Receptors, Immunologic / immunology
  • Recombinant Proteins / genetics
  • Recombinant Proteins / immunology
  • Recombinant Proteins / metabolism
  • Swine
  • Transfection
  • Transplantation, Heterologous / immunology

Substances

  • Antigens, CD
  • Capsid Proteins
  • HLA Antigens
  • HLA-G Antigens
  • Histocompatibility Antigens Class I
  • LILRB1 protein, human
  • Leukocyte Immunoglobulin-like Receptor B1
  • Receptors, Immunologic
  • Recombinant Proteins
  • VP23 protein, Human herpesvirus 1
  • Interferon-gamma