MHC expression in a human adult stem cell line and its down-regulation by hCMV US gene transfection.
Due to their unique capacity to self-renew and for multiple differentiation, stem cells are considered promising candidates for cell replacement therapy in many devastating diseases. However, studies on immune rejection, which is a major problem facing successful stem cell therapy, are rare. In this study, we examined MHC expression in the M13SV1 cell line, which has previously been shown to have stem cell properties and to be non-tumorigenic, in order to determine whether human adult stem cells might be rejected after transplantation. Our results show low expression levels of MHC class I molecules on the surface of these cells. An induction of MHC class I expression was observed when the cells were treated with IFN-gamma. Maximal induction of MHC class protein expression was observed at 48 h after treatment with concentrations above 5 ng/ml of IFN-gamma. Elevated MHC class I levels were sustained for 72 h after withdrawing IFN-gamma. Therefore, we introduced human cytomegalovirus (hCMV) US genes, which are known to be able to reduce MHC class I expression on the cell surface after infection, into M13SV1 cells. Cells transfected with the hCMV US2, US3, US6 or US11 genes exhibited a reduction (40-60%) of MHC class I expression compared with mock-transfected cells. These results suggest that human adult stem cells are capable of expressing high levels of MHC class I proteins, and thus may be rejected on transplantation unless they are modified. In addition, viral stealth mechanisms can be exploited for stem cell transplantation.
Kim
Jae Young
JY
Xenotransplantation Research Center, Seoul National University Hospital, Seoul 110-744, South Korea.
Kim
Donghee
D
Choi
Inho
I
Yang
Jae Seok
JS
Lee
Dong-Sup
DS
Lee
Jeong Ryul
JR
Kang
Kyungsun
K
Kim
Seokhyun
S
Hwang
Woo Suk
WS
Lee
Jung Sang
JS
Ahn
Curie
C
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology; D002460:Cell Line; D003587:Cytomegalovirus / Q000235:genetics*; D015536:Down-Regulation / Q000235:genetics*; D015395:Histocompatibility Antigens Class I / Q000096:biosynthesis* / Q000235:genetics / Q000276:immunology; D006801:Humans; D007371:Interferon-gamma / Q000494:pharmacology; D033581:Stem Cell Transplantation; D013234:Stem Cells / Q000166:cytology / Q000276:immunology / Q000378:metabolism*; D014162:Transfection; D015854:Up-Regulation / Q000187:drug effects; D014764:Viral Proteins / Q000096:biosynthesis* / Q000235:genetics
D000970:Antineoplastic Agents; D015395:Histocompatibility Antigens Class I; D014764:Viral Proteins; D007371:Interferon-gamma