title: Different roles of PD-L1 and FasL in immunomodulation mediated by human placenta-derived mesenchymal stem cells.
abstract: Mesenchymal stem cells (MSCs) derived from either bone marrow (BMSCs) or placenta (PMSCs) have the capacity to suppress immune responses to mitogenic and allogeneic stimulations. Both cell contact and soluble factor dependent mechanisms have been proposed to explain this immunosuppression. This study explored the roles of some of cell surface molecules expressed on human PMSCs (hPMSCs) in hPMSC mediated immunomodulation. hPMSCs strongly suppressed mitogen and allogeneic peripheral mononuclear cells (PBMCs) induced T cell activation and proliferation. hPMSCs constituently expressed programmed death-ligand 1 (PD-L1) and Fas ligand (FasL) molecules. Neutralising antibodies to-PD-L1 and FasL significantly reduced the suppressive effect of hPMSCs on T cell proliferation. However, only anti-PD-L1 antibody partially restored early T cell activation suppressed by hPMSCs. Anti-FasL antibody but not anti-PD-L1 antibody reduced apoptosis of activated T cell indicating that FasL molecule plays a role in inducing apoptosis of activated T cells, although overall hPMSCs diminished T cell apoptosis. Different effects of PD-L1 and FasL molecules on T cell activation and activated T cell apoptosis suggest that these two molecules influence T cell response at different stages. hPMSCs significantly prevented activated T cells from going into S phase. Both antibodies to PD-L1 and FasL had significant effect on reversing the effect of hPMSCs on cell cycles. hPMSCs reduced INF-γ but increased IL-10 production by mitogen activated T cells. Both antibodies partially abolished the effect of hPMSCs on INF-γ and IL-10 production. These data demonstrated that PD-L1 and FasL molecules play significant roles in immunomodulation mediated by hPMSCs. This study provides a rational basis for modulation of negative costimulators on hPMSCs to increase their immunosuppressive properties in their therapeutic applications.
authors.affiliation: Jiangsu Institute of Clinical Immunology, The First Affiliated Hospital of Soochow University, Suzhou, People's Republic of China.
authors.forename: Yan-zheng
authors.initials: YZ
authors.lastname: Gu
authors.forename: Qun
authors.initials: Q
authors.lastname: Xue
authors.forename: Yong-jing
authors.initials: YJ
authors.lastname: Chen
authors.forename: Ge-Hua
authors.initials: GH
authors.lastname: Yu
authors.forename: Ming-de
authors.initials: MD
authors.lastname: Qing
authors.forename: Yu
authors.initials: Y
authors.lastname: Shen
authors.forename: Ming-yuan
authors.initials: MY
authors.lastname: Wang
authors.forename: Qin
authors.initials: Q
authors.lastname: Shi
authors.forename: Xue-Guang
authors.initials: XG
authors.lastname: Zhang
mesh_terms: D000911:Antibodies, Monoclonal / Q000276:immunology / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects / Q000276:immunology; D060890:B7-H1 Antigen / Q000276:immunology* / Q000378:metabolism; D002453:Cell Cycle / Q000187:drug effects / Q000276:immunology; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D018920:Coculture Techniques; D004305:Dose-Response Relationship, Drug; D053222:Fas Ligand Protein / Q000276:immunology* / Q000378:metabolism; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D007371:Interferon-gamma / Q000276:immunology / Q000378:metabolism; D016753:Interleukin-10 / Q000276:immunology / Q000378:metabolism; D007963:Leukocytes, Mononuclear / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D008213:Lymphocyte Activation / Q000276:immunology; D059630:Mesenchymal Stem Cells / Q000276:immunology* / Q000378:metabolism; D008856:Microscopy, Fluorescence; D010835:Phytohemagglutinins / Q000276:immunology / Q000494:pharmacology; D010920:Placenta / Q000166:cytology*; D011247:Pregnancy; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism
chemical_list: D000911:Antibodies, Monoclonal; D060890:B7-H1 Antigen; C423236:CD274 protein, human; D053222:Fas Ligand Protein; D010835:Phytohemagglutinins; D016753:Interleukin-10; D007371:Interferon-gamma