Surface expression of HLA-G is involved in mediating immunomodulatory effects of placenta-derived multipotent cells (PDMCs) towards natural killer lymphocytes

Ko Jiunn Liu, Chia Jen Wang, Chan Jung Chang, Hsin I. Hu, Pei Ju Hsu, Yu Chen Wu, Chyi Huey Bai, Huey Kang Sytwu, B. Linju Yen

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28 Citations (Scopus)


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

Original languageEnglish
Pages (from-to)1721-1730
Number of pages10
JournalCell Transplantation
Issue number11-12
Publication statusPublished - 2011



  • HLA-G
  • Immunomodulation
  • Mesenchymal stem cells (MSCs)
  • Natural killer lymphocytes
  • Placenta

ASJC Scopus subject areas

  • Cell Biology
  • Transplantation
  • Biomedical Engineering

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