Down-regulation of MHC class I expression in human neuronal stem cells using viral stealth mechanism

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Lee, Eun Mi; Kim, Jae Young; Cho, Bum Rae; Chung, Woo Kyung; Yoon, Byung-Woo; Kim, Seung U; Lee, Byeong Chun; Hwang, Woo Suk; Moon, Shin-Yong; Lee, Jung Sang; Ahn, Curie
Issue Date
Biochem Biophys Res Commun. 2005 Jan 28;326(4):825-35.
Cell LineCytomegalovirus/genetics/*metabolismDown-Regulation/drug effects/immunologyFeasibility StudiesGenetic Enhancement/methodsHistocompatibility Antigens Class I/immunology/*metabolismHumansMembrane Glycoproteins/genetics/immunology/*metabolismNeurons/cytology/immunology/*metabolismStem Cells/cytology/immunology/*metabolismTransfection/*methodsViral Proteins/genetics/immunology/*metabolism
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 48h 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 72h 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.
0006-291X (Print)
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College of Medicine/School of Medicine (의과대학/대학원)Obstetrics & Gynecology (산부인과전공)Journal Papers (저널논문_산부인과학전공)
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