T-cell activation response to allogeneic CMV-infected endothelial cells is not prevented by ganciclovir or foscarnet: implications for transplant vascular sclerosis.
T-cell activation response to allogeneic CMV-infected endothelial cells is not prevented by ganciclovir or foscarnet: implications for transplant vascular sclerosis.
复制标题
更昔洛韦或膦甲酸不能阻止对同种异体 CMV 感染的内皮细胞的 T 细胞激活反应：对移植血管硬化的影响。
DOI：
10.1097/00007890-200201270-00032
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发表时间：
2002
期刊：
影响因子：
6.2
通讯作者：
Knight,DeborahA
中科院分区：
文献类型：
--
作者：
Waldman,WJames;LeClaire,JoshuaD;Knight,DeborahA
背景：巨细胞病毒(CMV)是移植受者常见的感染性并发症，已被认为是移植血管硬化症(TVS)的恶化因素；然而，其作用机制仍未完全解决。我们以前的研究表明，CMV感染的移植物内皮细胞(EC)可以启动宿主T细胞激活级联反应，因此产生的细胞因子可以增强移植物内皮细胞的同种免疫原性。由于抗病毒治疗并未统一降低发生TVS的风险，我们验证了抗病毒药物不影响同种异体CMV感染的EC激活T细胞的假设。方法将接种了CMV VHL/E的人脐静脉内皮细胞在有或无更昔洛韦(GCV)或磷甲酸钠(PFA)的情况下与CMV血清阳性或血清阴性供者来源的T细胞共同培养，然后标记[3 H]胸腺嘧啶核苷。结果：限制性稀释分析显示，GCV(约86个/106个细胞)或PFA(约82个/106个细胞)对CMV感染的EC的增殖频率(约80个细胞/106个，而对未感染的EC约为4个/106个细胞)没有明显的影响。结论：这些实验的结果表明，尽管这些药物限制了CMV的复制和传播，但它们并没有减弱感染的EC的炎症潜能，这可能是CMV介导的TVS发展加剧的一个主要因素。
Background.Cytomegalovirus (CMV), a common infectious complication in transplant recipients, has been implicated as an exacerbating agent in the development of transplant vascular sclerosis (TVS); however, mechanisms defining this role remain to be fully resolved. Our previous studies suggest that CMV-infected graft endothelial cells (EC) can initiate a host T-cell activation cascade, and that cytokines produced as a consequence enhance graft endothelial alloimmunogenicity. Because antiviral therapy has not uniformly attenuated CMV-associated risk of TVS development, we have tested the hypothesis that antiviral agents do not affect T-cell activation by allogeneic CMV-infected EC.Methods.Human umbilical vein EC, inoculated with CMV VHL/E and incubated in the presence or absence of ganciclovir (GCV) or foscarnet (PFA), were cocultured with CMV-seropositive or-seronegative donor-derived T cells in the presence of these agents, then labeled with [3 H] thymidine. Cocultures were harvested, and radiolabel incorporation was assayed by scintillation counting.Results.Limiting dilution analysis demonstrated that proliferation frequencies of CMV-seropositive donor-derived T cells in response to CMV-infected EC (approximately 80 cells/10 6, compared with approximately 4 cells/10 6 in response to uninfected EC) were not significantly modified by GCV (approximately 86 cells/10 6) or PFA (approximately 82 cells/10 6). Likewise, T-cell proliferation curves generated in response to stimulator cell titrations were essentially identical regardless of drug treatment.Conclusions.Results of these experiments suggest that although these drugs limit CMV replication and dissemination, they do not attenuate the inflammatory potential of infected EC, a force that may be a major factor in CMV-mediated exacerbation of the development of TVS.