Different roles of PD-L1 and FasL in immunomodulation mediated by human placenta-derived mesenchymal stem cells
Different roles of PD-L1 and FasL in immunomodulation mediated by human placenta-derived mesenchymal stem cells
复制标题
DOI：
10.1016/j.humimm.2012.12.011
复制
发表时间：
2013-03-01
期刊：
影响因子：
2.7
通讯作者：
Zhang, Xue-Guang
中科院分区：
文献类型：
--
作者：
Gu, Yan-zheng;Xue, Qun;Zhang, Xue-Guang
来自骨髓（BMSCs）或胎盘（PMSCs）的间充质干细胞（MSCs）具有抑制对有丝分裂和异体刺激的免疫反应的能力。细胞接触和可溶性因子依赖机制都被提出来解释这种免疫抑制。本研究探讨了人PMSCs （hPMSCs）上表达的一些细胞表面分子在hPMSC介导的免疫调节中的作用。hPMSCs强烈抑制丝裂原和异基因外周单核细胞（PBMCs）诱导的T细胞活化和增殖。hPMSCs组成表达程序性死亡配体1 （PD-L1）和Fas配体（FasL）分子。中和pd - l1和FasL抗体显著降低hPMSCs对T细胞增殖的抑制作用。然而，只有抗pd - l1抗体能部分恢复hPMSCs抑制的早期T细胞活化。抗FasL抗体而非抗pd - l1抗体减少了活化T细胞的凋亡，表明FasL分子在诱导活化T细胞凋亡中起作用，尽管总体上hPMSCs减少了T细胞的凋亡。PD-L1和FasL分子对T细胞活化和活化T细胞凋亡的影响不同，说明这两种分子在不同阶段影响T细胞应答。hPMSCs显著阻止活化T细胞进入S期。PD-L1和FasL抗体均能显著逆转hPMSCs对细胞周期的影响。hPMSCs减少了有丝分裂原激活T细胞的inf - γ，但增加了IL-10的产生。这两种抗体都部分消除了hPMSCs对inf - γ和IL-10产生的影响。这些数据表明，PD-L1和FasL分子在hPMSCs介导的免疫调节中发挥重要作用。本研究为调节负性共刺激剂对hPMSCs的免疫抑制作用提供了合理的基础。(c) 2012年美国组织相容性和免疫遗传学学会。Elsevier Inc.出版。版权所有。
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-gamma but increased IL-10 production by mitogen activated T cells. Both antibodies partially abolished the effect of hPMSCs on INF-gamma 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. (c) 2012 American Society for Histocompatibility and Immunogenetics. Published by Elsevier Inc. All rights reserved.