title: Immunosuppressive mechanisms of embryonic stem cells and mesenchymal stem cells in alloimmune response.
abstract: Although both embryonic stem cells (ESCs) and mesenchymal stem cells (MSCs) are known to have immunosuppressive effects, the mechanisms of immunosuppression are still controversial. Both types of stem cells suppressed not only the proliferation but also survival of CD4(+) T cells in vitro. They suppressed secretion of various cytokines (IL-2, IL-12, IFN-γ, TNF-α, IL-4, IL-5, IL-1β, and IL-10), whereas there was no change in the levels of TGF-β or IDO. Classic and modified transwell experiments demonstrated that immunosuppressive activities were mainly mediated by cell-to-cell contact. Granzyme B in the ESCs played a significant role in their immunosuppression, whereas PDL-1, Fas ligand, CD30 or perforin was not involved in the contact-dependent immunosuppression. However, none of the above molecules played a significant role in the immunosuppression by the MSCs. Interestingly, both stem cells increased the proportion of Foxp3(+) regulatory T cells. Our results showed that both ESCs and MSCs suppressed the survival as well as the proliferation of T cells by mainly contact-dependent mechanisms and increased the proportion of regulatory T cells. Granzyme B was involved in immunosuppression by the ESCs in a perforin-independent manner.
authors.affiliation: Transplantation Research Institute, Seoul National University College of Medicine, Seoul, Republic of Korea.
authors.forename: Kyu Hyun
authors.initials: KH
authors.lastname: Han
authors.forename: Han
authors.initials: H
authors.lastname: Ro
authors.forename: Ju Ho
authors.initials: JH
authors.lastname: Hong
authors.forename: Eun Mi
authors.initials: EM
authors.lastname: Lee
authors.forename: Bumrae
authors.initials: B
authors.lastname: Cho
authors.forename: Hye Jung
authors.initials: HJ
authors.lastname: Yeom
authors.forename: Myung-Gyu
authors.initials: MG
authors.lastname: Kim
authors.forename: Kook-Hwan
authors.initials: KH
authors.lastname: Oh
authors.forename: Curie
authors.initials: C
authors.lastname: Ahn
authors.forename: Jaeseok
authors.initials: J
authors.lastname: Yang
mesh_terms: D000818:Animals; D049109:Cell Proliferation; D002470:Cell Survival / Q000276:immunology; D002478:Cells, Cultured; D016207:Cytokines / Q000276:immunology; D053595:Embryonic Stem Cells / Q000166:cytology / Q000276:immunology*; D053222:Fas Ligand Protein / Q000276:immunology; D053804:Granzymes / Q000276:immunology; D007108:Immune Tolerance; D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase / Q000276:immunology; D017730:Ki-1 Antigen / Q000276:immunology; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D052899:Pore Forming Cytotoxic Proteins / Q000276:immunology; D050378:T-Lymphocytes, Regulatory / Q000276:immunology
chemical_list: D016207:Cytokines; D053222:Fas Ligand Protein; D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase; D017730:Ki-1 Antigen; D052899:Pore Forming Cytotoxic Proteins; C483886:perforin, mouse; D053804:Granzymes