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