Human cytomegalovirus UL18 alleviated human NK-mediated swine endothelial cell lysis
Human cytomegalovirus UL18 alleviated human NK-mediated swine endothelial cell lysis
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DOI：
10.1016/j.bbrc.2004.01.027
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发表时间：
2004-02-27
影响因子：
3.1
通讯作者：
Park, CG
中科院分区：
文献类型：
--
作者：
Kim, JS;Choi, SE;Park, CG
已知人巨细胞病毒UL 18（MHC I类同源物）充当自然杀伤细胞（NK）诱饵并连接NK抑制性受体以防止感染的靶细胞裂解。为了探索UL 18的细胞表面表达是否代表在异种移植排斥的预防中逃避NK介导的细胞毒性的潜在免疫抑制方法，我们检查了UL 18表达在体外对人NK介导的针对猪内皮细胞（SEC）的细胞毒性的影响。通过逆转录病毒载体（PLNCX 2）在SEC上的UL 18表达显著抑制NK介导的SEC裂解约25- 100%。UL 18的保护作用可能是通过抑制NK细胞上的ILT-2受体而实现的。此外，UL 18和NK之间的相互作用导致IFN-γ产生的显著减少。这项研究表明，UL 18可以作为一种有效的工具，用于逃避NK介导的细胞毒性和抑制IFN-γ的产生在异种移植排斥反应。(C)2004年爱思唯尔公司All rights reserved.
Human cytomegalovirus UL 18, 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 UL 18 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 UL 18 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. (C) 2004 Elsevier Inc. All rights reserved.