title: Surface expression of HLA-G is involved in mediating immunomodulatory effects of placenta-derived multipotent cells (PDMCs) towards natural killer lymphocytes.
abstract: Interactions between maternal natural killer lymphocytes (NKs) and fetal tissues are important in mediating maternal-fetal tolerance. We therefore investigated the interactions of NKs to placenta-derived multipotent cells (PDMCs) isolated from the term human placenta. PDMCs have similar cell surface marker expression as bone marrow mesenchymal stem cells (BMMSCs) and additionally express human embryonic stem cell markers SSEA-4 and CD-9. Differentiation into the tri-mesodermal lineages of osteoblastic, adipocytic, and chondrogenic phenotypes can be readily achieved under the appropriate conditions. We found that PDMCs are more resistant to NK-mediated lysis than the major histocompatibility complex (MHC) class-I null target cell K562, and can suppress NK secretion of interferon-γ (IFN-γ). Moreover, as third-party cells, PDMCs suppressed the cytotoxic effects of cytokine-stimulated NKs on K562. Pretreatment of PDMCs with IFN-γ, a proinflammatory cytokine, surprisingly enhanced such immunosuppressive effects. Cell-cell contact between NKs and PDMCs is required for suppressive effects, which are partially mediated by slight upregulation of the NK inhibitory receptor killer inhibitory receptor and downregulation of the activating receptor NKp30. Moreover, enhancement of PDMC suppressive effects is also mediated by IFN-γ-induced surface expression of HLA-G--an immunomodulatory nonclassical MHC class I molecule--on PDMCs, as seen by partial reversibility with HLA-G neutralizing antibodies. With its broad immunosuppressive properties, PDMCs may represent a potential cell source for therapeutic use.
authors.affiliation: National Institute of Cancer Research, National Health Research Institutes, Tainan, Taiwan.
authors.forename: Ko-Jiunn
authors.initials: KJ
authors.lastname: Liu
authors.forename: Chia-Jen
authors.initials: CJ
authors.lastname: Wang
authors.forename: Chan-Jung
authors.initials: CJ
authors.lastname: Chang
authors.forename: Hsin-I
authors.initials: HI
authors.lastname: Hu
authors.forename: Pei-Ju
authors.initials: PJ
authors.lastname: Hsu
authors.forename: Yu-Chen
authors.initials: YC
authors.lastname: Wu
authors.forename: Chyi-Huey
authors.initials: CH
authors.lastname: Bai
authors.forename: Huey-Kang
authors.initials: HK
authors.lastname: Sytwu
authors.forename: B Linju
authors.initials: BL
authors.lastname: Yen
mesh_terms: D002454:Cell Differentiation; D002478:Cells, Cultured; D003602:Cytotoxicity, Immunologic / Q000187:drug effects; D005260:Female; D059951:HLA-G Antigens / Q000276:immunology / Q000378:metabolism*; D006801:Humans; D007165:Immunosuppression Therapy; D007371:Interferon-gamma / Q000494:pharmacology; D007376:Interleukin-2 / Q000494:pharmacology; D020014:K562 Cells; D007694:Killer Cells, Natural / Q000276:immunology*; D039902:Multipotent Stem Cells / Q000166:cytology / Q000276:immunology / Q000378:metabolism*; D055628:Natural Cytotoxicity Triggering Receptor 3 / Q000378:metabolism; D010920:Placenta / Q000166:cytology*; D011247:Pregnancy; D011956:Receptors, Cell Surface / Q000378:metabolism
chemical_list: D059951:HLA-G Antigens; D007376:Interleukin-2; C431710:NCR3 protein, human; D055628:Natural Cytotoxicity Triggering Receptor 3; D011956:Receptors, Cell Surface; D007371:Interferon-gamma