Human cytomegalovirus UL18 alleviated human NK-mediated swine endothelial cell lysis.
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.
Kim
Jung-Sik
JS
Department of Microbiology and Immunology, Seoul National University College of Medicine, Seoul 110-799, Republic of Korea.
Choi
Seung-Eun
SE
Yun
Il-Hee
IH
Kim
Jae-Young
JY
Ahn
Curie
C
Kim
Sang-Joon
SJ
Ha
Jongwon
J
Hwang
Eung-Soo
ES
Cha
Chang-Yong
CY
Miyagawa
Shuji
S
Park
Chung-Gyu
CG
D000818:Animals; D015703:Antigens, CD / Q000096:biosynthesis / Q000276:immunology; D036022:Capsid Proteins / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D002460:Cell Line; D002462:Cell Membrane / Q000276:immunology / Q000378:metabolism; D003602:Cytotoxicity, Immunologic; D004730:Endothelium, Vascular / Q000166:cytology / Q000276:immunology* / Q000637:transplantation / Q000821:virology; D005434:Flow Cytometry; D019084:Fluorescent Antibody Technique, Indirect; D006680:HLA Antigens / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology; D059951:HLA-G Antigens; D015395:Histocompatibility Antigens Class I / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology; D006801:Humans; D007371:Interferon-gamma / Q000378:metabolism; D007694:Killer Cells, Natural / Q000276:immunology*; D000075362:Leukocyte Immunoglobulin-like Receptor B1; D011971:Receptors, Immunologic / Q000096:biosynthesis / Q000276:immunology; D011994:Recombinant Proteins / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D013552:Swine; D014162:Transfection; D014183:Transplantation, Heterologous / Q000276:immunology
D015703:Antigens, CD; D036022:Capsid Proteins; D006680:HLA Antigens; D059951:HLA-G Antigens; D015395:Histocompatibility Antigens Class I; C105299:LILRB1 protein, human; D000075362:Leukocyte Immunoglobulin-like Receptor B1; D011971:Receptors, Immunologic; D011994:Recombinant Proteins; C079750:VP23 protein, Human herpesvirus 1; D007371:Interferon-gamma