Low immunogenicity of endothelial derivatives from rat embryonic stem cell-like cells.
Embryonic stem cells (ESC) are suggested to be immune-privileged, but they carry the risk of uncontrolled expansion and malignancy. Upon differentiation they lose their tumor-forming capacity, but they become immunogenic by the expression of a normal set of MHC molecules. This immunogenicity might trigger rejection after application in regenerative therapies. In this study MHC expression of and immune responses to endothelial derivatives of rat embryonic stem cell-like cells (RESC) under inflammatory conditions were determined in comparison to primary rat aortic endothelial cells (ECs). Cellular as well as humoral allo-recognition was analyzed in vitro. In addition, immune reactions in vivo were assessed by allo-antibody production and determination of interferon-gamma (IFNgamma)-secreting allo-reactive T cells. RESC derivatives expressed low but significant levels of MHC class I, and no MHC class II. In response to IFNgamma MHC class I expression was enhanced, while class II transactivator induction failed completely in these cells; MHC class II expression remained consistently absent. Functionally, the RESC derivatives showed a reduced allo-stimulatory capacity, protection against humoral allo-recognition in vitro and a slightly diminished susceptibility to cytotoxic T cell lysis. Furthermore, in vivo experiments demonstrated that these cells do not trigger host immune reactions, characterized by no allo-antibody production and no induction of allo-reactive memory T cells. Our results show that endothelial derivatives of RESC have a distinctive reduced immunogenic potency even under inflammatory conditions.
Ladhoff
Juliane
J
Institute of Medical Immunology, Charité Universitätsmedizin Berlin, Campus Charité Mitte, Monbijoustrasse 2a, 10117 Berlin, Germany.
Bader
Michael
M
Brösel
Sabine
S
Effenberger
Elke
E
Westermann
Dirk
D
Volk
Hans-Dieter
HD
Seifert
Martina
M
D000818:Animals; D002454:Cell Differentiation; D053595:Embryonic Stem Cells / Q000276:immunology*; D042783:Endothelial Cells / Q000276:immunology*; D015395:Histocompatibility Antigens Class I / Q000276:immunology / Q000378:metabolism; D000949:Histocompatibility Antigens Class II / Q000276:immunology / Q000378:metabolism; D007114:Immunization; D007371:Interferon-gamma / Q000378:metabolism / Q000494:pharmacology; D007518:Isoantibodies / Q000378:metabolism; D051381:Rats; D015398:Signal Transduction; D013601:T-Lymphocytes / Q000276:immunology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology
D015395:Histocompatibility Antigens Class I; D000949:Histocompatibility Antigens Class II; D007518:Isoantibodies; D007371:Interferon-gamma