Down-regulation of MHC class I expression in human neuronal stem cells using viral stealth mechanism.
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.
Lee
Eun Mi
EM
Stem Cell Laboratory in Clinical Research Institute and Xenotransplantation Research Center, Seoul National University Hospital, Seoul 110-744, Republic of Korea.
Kim
Jae Young
JY
Cho
Bum Rae
BR
Chung
Woo Kyung
WK
Yoon
Byung-Woo
BW
Kim
Seung U
SU
Lee
Byeong Chun
BC
Hwang
Woo Suk
WS
Moon
Shin-Yong
SY
Lee
Jung Sang
JS
Ahn
Curie
C
D002460:Cell Line; D003587:Cytomegalovirus / Q000235:genetics / Q000378:metabolism*; D015536:Down-Regulation / Q000187:drug effects / Q000276:immunology; D005240:Feasibility Studies; D024861:Genetic Enhancement / Q000379:methods; D015395:Histocompatibility Antigens Class I / Q000276:immunology / Q000378:metabolism*; D006801:Humans; D008562:Membrane Glycoproteins / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D009474:Neurons / Q000166:cytology / Q000276:immunology / Q000378:metabolism*; D013234:Stem Cells / Q000166:cytology / Q000276:immunology / Q000378:metabolism*; D014162:Transfection / Q000379:methods*; D014764:Viral Proteins / Q000235:genetics / Q000276:immunology / Q000378:metabolism*
D015395:Histocompatibility Antigens Class I; D008562:Membrane Glycoproteins; D014764:Viral Proteins