Characterization of the expression of MHC proteins in human embryonic stem cells.
Human embryonic stem (ES) cells are pluripotent cells that may be used in transplantation medicine. These cells can be induced to differentiate into cells from the three embryonic germ layers both in vivo and in vitro. To determine whether human ES cells might be rejected after transplantation, we examined cell surface expression of the MHC proteins in these cells. Our results show very low expression levels of MHC class I (MHC-I) proteins on the surface of human ES cells that moderately increase on in vitro or in vivo differentiation. A dramatic induction of MHC-I proteins was observed when the cells were treated with IFN-gamma but not with IFN-alpha or -beta. However, all three IFNs induced expression of MHC-I proteins in differentiated human ES cells. MHC-II proteins and HLA-G were not expressed on the surface of undifferentiated or differentiated cells. Ligands for natural killer cell receptors were either absent or expressed in very low levels in human ES cells and in their differentiated derivatives. In accordance, natural killer cytotoxic assays demonstrated only limited lysis of both undifferentiated and differentiated cells. To initiate a histocompatibility databank of human ES cells, we have isotyped several of the published ES cell lines for their human leukocyte antigens. In conclusion, our results demonstrate that human ES cells can express high levels of MHC-I proteins and thus may be rejected on transplantation.
Department of Genetics, Silberman Institute of Life Sciences, Hebrew University, 91904 Jerusalem, Israel.
Micha
M
Drukker
Gil
G
Katz
Achia
A
Urbach
Maya
M
Schuldiner
Gal
G
Markel
Joseph
J
Itskovitz-Eldor
Benjamin
B
Reubinoff
Ofer
O
Mandelboim
Nissim
N
Benvenisty
D002454:Cell Differentiation; D016208:Databases, Factual; D004622:Embryo, Mammalian; D005786:Gene Expression Regulation / Q000276:immunology; D006681:HLA-D Antigens / Q000032:analysis / Q000235:genetics*; D015395:Histocompatibility Antigens Class I / Q000032:analysis / Q000235:genetics*; D006650:Histocompatibility Testing; D006801:Humans; D007371:Interferon-gamma / Q000494:pharmacology; D007700:Kinetics; D008285:Major Histocompatibility Complex; D013234:Stem Cells / Q000166:cytology / Q000187:drug effects / Q000276:immunology*
D006681:HLA-D Antigens; D015395:Histocompatibility Antigens Class I; D007371:Interferon-gamma