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
Department of Microbiology and Immunology, Seoul National University College of Medicine, Seoul 110-799, Republic of Korea.
Biochem Biophys Res Commun. 2004 Feb 27;315(1):144-50. doi: 10.1016/j.bbrc.2004.01.027.
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.
人巨细胞病毒UL18是一种I类主要组织相容性复合体（MHC）同源物，已知它可作为自然杀伤细胞（NK）的诱饵，并与NK抑制性受体结合，以防止感染的靶细胞被裂解。为了探究UL18的细胞表面表达是否代表一种潜在的免疫抑制方法，以在预防异种移植排斥反应中逃避NK介导的细胞毒性，我们在体外检测了UL18表达对人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（PLNCX2）使SEC表达UL18，可显著抑制NK介导的SEC裂解，抑制率约为25%-100%。UL18的保护作用可能通过NK细胞上的ILT-2抑制性受体介导。此外，UL18与NK细胞之间的相互作用导致干扰素-γ（IFN-γ）产生显著减少。本研究表明，UL18可作为一种有效工具，用于在异种移植排斥反应中逃避NK介导的细胞毒性并抑制IFN-γ产生。
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