National Institute of Cancer Research, National Health Research Institutes, Tainan, Taiwan.
Cell Transplant. 2011;20(11-12):1721-30. doi: 10.3727/096368911X580590. Epub 2011 Jun 9.
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.
自然杀伤细胞（NK）与胎儿组织之间的相互作用在介导母胎耐受中起着重要作用。因此，我们研究了 NK 与从足月人胎盘分离的多能细胞（PDMC）的相互作用。PDMC 具有与骨髓间充质干细胞（BMMSC）相似的细胞表面标志物表达，并且还表达人类胚胎干细胞标志物 SSEA-4 和 CD-9。在适当的条件下，很容易将其分化为成骨细胞、脂肪细胞和成软骨细胞的三胚层谱系。我们发现 PDMC 比主要组织相容性复合体（MHC）I 类缺失靶细胞 K562 更能抵抗 NK 介导的裂解，并且可以抑制 NK 分泌干扰素-γ（IFN-γ）。此外，作为第三方细胞，PDMC 抑制细胞因子刺激的 NK 对 K562 的细胞毒性作用。PDMC 用 IFN-γ预处理，一种促炎细胞因子，出人意料地增强了这种免疫抑制作用。NK 和 PDMC 之间的细胞接触对于抑制作用是必需的，这部分是通过稍微上调 NK 抑制受体杀伤抑制受体和下调激活受体 NKp30 来介导的。此外，PDMC 抑制作用的增强也由 IFN-γ诱导的 PDMC 表面 HLA-G 的表达介导，这是通过 HLA-G 中和抗体的部分可逆性来观察到的。PDMC 具有广泛的免疫抑制特性，可能代表一种潜在的治疗用途的细胞来源。
