Human cytomegalovirus UL18 alleviated human NK-mediated swine endothelial cell lysis |
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Authors: | Kim Jung-Sik Choi Seung-Eun Yun Il-Hee Kim Jae-Young Ahn Curie Kim Sang-Joon Ha Jongwon Hwang Eung-Soo Cha Chang-Yong Miyagawa Shuji Park Chung-Gyu |
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Affiliation: | Department of Microbiology and Immunology, Seoul National University College of Medicine, Seoul 110-799, Republic of Korea. |
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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. |
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Keywords: | Human cytomegalovirus UL18 Natural killer cell IFN-γ Xenograft rejection Swine endothelial cell ILT-2 YT cell line |
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