Down-regulation of MHC class I expression in human neuronal stem cells using viral stealth mechanism
Down-regulation of MHC class I expression in human neuronal stem cells using viral stealth mechanism
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DOI：
10.1016/j.bbrc.2004.11.106
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发表时间：
2005-01-28
影响因子：
3.1
通讯作者：
Ahn, C
中科院分区：
文献类型：
--
作者：
Lee, EM;Kim, JY;Ahn, C
由于其独特的自我更新能力以及分化为所有神经元谱系细胞的能力，神经元干细胞（NSC）是神经元损伤和神经退行性疾病细胞替代疗法的有希望的候选者。然而，关于免疫排斥的研究很少，这是成功干细胞治疗面临的主要问题之一。为了确定移植后人类 NSC 是否可能被排斥，对 HB1.F3 细胞系中的 MHC 表达水平进行了检查，该细胞系先前已被证明表现出 NSC 特性。结果显示这些细胞表面 MHC I 类分子的表达水平较低。当用IFN-γ、TNF-α和IL-1β单独或组合处理细胞时，观察到MHC I类表达水平显着增加。治疗后，在高于20ng/ml IFN-γ 48 It时观察到MHC I类蛋白表达的最大诱导。没有观察到TNF-α和IL-1β组合对IFN-γ治疗所发挥的MHC I类表达的最大诱导作用的明显累加效应。 IFN-γ 导致的 MHC I 类水平在撤除 IFN-γ 后持续 72 小时。因此，本研究将人类巨细胞病毒（hCMV）US基因引入HB1.F3细胞中，该基因已知能够降低感染后细胞表面MHC I类表达水平。与模拟转染的细胞相比，用hCMV US2、US3、US6或US11基因转染的细胞显示MHC I类表达水平降低20-50%。这些结果表明 NSC 表达高水平的 MHC I 类蛋白，除非对其进行修饰，否则可能会在移植时被排斥。此外，各种病毒隐形机制可用于干细胞移植。 (C) 2004 Elsevier Inc. 保留所有权利。
Due to their unique capacity for self-renewal in addition to their ability to differentiate into cells of all neuronal lineages, neuronal stem cells (NSCs) are promising candidates for cell replacement therapy in neuronal injury and neurodegenerative diseases. However, there are few studies on immune rejection, which is one of the main problems facing successful stem cell therapy. In order to determine if human NSC might be rejected after transplantation the MHC expression level was examined in the HB1.F3 cell line, which has previously been shown to exhibit NSC properties. The results showed low expression levels of the MHC class I molecules on the surfaces of these cells. A dramatic increase in the MHC class I expression level was observed when the cells were treated with IFN-gamma, TNF-alpha, and IL-1beta, alone or in combination. The maximum induction of MHC class I protein expression was observed at above 20ng/ml IFN-gamma 48 It after the treatment. The apparent additive effects of TNF-alpha and IL-1beta in combination on the maximum induction of MHC class I expression exerted by IFN-gamma treatment were not observed. The MHC class I levels elevated by IFN-gamma were sustained for 72 h after withdrawing the IFN-gamma. Therefore, this study introduced human cytomegalovirus (hCMV) US genes, which are known to be able to reduce the MHC class I expression level on the cell surface after infection, into HB1.F3 cells. The cells transfected with the hCMV US2, US3, US6 or US11 genes showed 20-50% reduction in the MHC class I expression level compared with the mock-transfected cells. These results suggest that NSC expresses high levels of the MHC class I proteins, and unless they are modified, might be rejected upon transplantation. In addition, the various viral stealth mechanisms can be exploited for stem cell transplantation. (C) 2004 Elsevier Inc. All rights reserved.