title: Human embryonic stem cells and their differentiated derivatives are less susceptible to immune rejection than adult cells.
abstract: Differentiated cell types derived from human embryonic stem cells (hESCs) may serve in the future to treat various human diseases. A crucial step toward their successful clinical application is to examine the immune response that might be launched against them after transplantation. We used two experimental platforms to examine the in vivo leukocyte response toward hESCs. First, immunocompetent and immunodeficient mouse strains were used to identify T cells as the major component that causes xenorejection of hESCs. Second, mice that were conditioned to carry peripheral blood leukocytes from human origin were used to test the human leukocyte alloresponse toward undifferentiated and differentiated hESCs. Using this model, we have detected only a minute immune response toward undifferentiated as well as differentiated hESCs over the course of 1 month, although control adult grafts were repeatedly infiltrated with lymphocytes and destroyed. Our data show that the cells evade immune destruction due to a low immunostimulatory potential. Nevertheless, a human cytotoxic T lymphocyte clone that was specifically prepared to recognize two hESC lines could lyse the cells after major histocompatibility complex class I (MHC-I) induction. Although MHC-I levels in hESCs are sufficient for rejection by cytotoxic T cells, our data suggest that the immunostimulatory capacity of the cells is very low. Thus, immunosuppressive regimens for hESC-based therapeutics could be highly reduced compared with conventional organ transplantation because direct allorejection processes of hESCs and their derivatives are considerably weaker.
authors.affiliation: Department of Genetics, Silberman Institute of Life Sciences, The Hebrew University, 91904 Jerusalem, Israel. dmicha@mail.ls.huji.ac.il
authors.forename: Micha
authors.initials: M
authors.lastname: Drukker
authors.forename: Helena
authors.initials: H
authors.lastname: Katchman
authors.forename: Gil
authors.initials: G
authors.lastname: Katz
authors.forename: Smadar
authors.initials: S
authors.lastname: Even-Tov Friedman
authors.forename: Elias
authors.initials: E
authors.lastname: Shezen
authors.forename: Eran
authors.initials: E
authors.lastname: Hornstein
authors.forename: Ofer
authors.initials: O
authors.lastname: Mandelboim
authors.forename: Yair
authors.initials: Y
authors.lastname: Reisner
authors.forename: Nissim
authors.initials: N
authors.lastname: Benvenisty
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000276:immunology*; D004622:Embryo, Mammalian / Q000166:cytology*; D053222:Fas Ligand Protein; D020869:Gene Expression Profiling; D006084:Graft Rejection / Q000209:etiology* / Q000276:immunology; D006801:Humans; D007121:Immunocompetence; D008562:Membrane Glycoproteins / Q000502:physiology; D051379:Mice; D008815:Mice, Inbred Strains; D008817:Mice, Mutant Strains; D016513:Mice, SCID / Q000276:immunology; D033581:Stem Cell Transplantation; D013234:Stem Cells / Q000276:immunology*; D016176:T-Lymphocyte Subsets / Q000502:physiology; D013602:T-Lymphocytes, Cytotoxic / Q000502:physiology; D014183:Transplantation, Heterologous; D048069:Tumor Necrosis Factors / Q000502:physiology
chemical_list: C505661:FASLG protein, human; D053222:Fas Ligand Protein; C505658:Fasl protein, mouse; D008562:Membrane Glycoproteins; D048069:Tumor Necrosis Factors