Department of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea.
Cytotherapy. 2012 Jan;14(1):70-9. doi: 10.3109/14653249.2011.613926. Epub 2011 Sep 28.
Mesenchymal stromal cells (MSC) from several tissues have immunomodulatory properties that involve various immunosuppressive molecules. An example is human leukocyte antigen (HLA)-G, a non-classical major histocompatibility complex (MHC) class I molecule that induces tolerance via interactions with inhibitory receptors present on major immune effector cells. Recently, the molecular mechanisms that regulate MSC-mediated immunosuppression have come under investigation. Our goal was to determine whether HLA-G plays a crucial role in immunosuppression and whether human adipose tissure (hAT) MSC can be used as a tool for biologic immunosuppression with HLA-G in transplantation.
MSC were characterized by fluorescence-activated cell sorting (FACS) analysis, reverse transcriptase (RT)-polymerase chain reaction (PCR) and staining for differentiation. The immunogenicity and immunomodulatory effects of MSC were monitored by peripheral blood mononuclear cell (PBMC) proliferation assay with or without phytohemagglutinin (PHA) stimulation. Stable expression of HLA-G1 in MSC was done using a lentiviral system. Results. MSC from different tissues had similar morphology, immunophenotypic characters and differentiation potential. We also found that the immunosuppressive effect of MSC was monitored along with their endogenous HLA-G mRNA and protein levels. Stable expression of HLA-G1 appeared to enhance the immunosuppressive effect of hAT MSC, and the function of HLA-G1 was significantly decreased by HLA-G antagonistic antibody in PBMC proliferation assays.
Although the HLA-G molecule is not the sole factor for MSC-mediated immunosuppression, our data provide evidence that HLA-G plays an important role in immunosuppression and that hAT MSC can be used as a tool for biologic immunosuppression during transplantation procedures.
来自多种组织的间充质基质细胞（MSC）具有免疫调节特性，涉及各种免疫抑制分子。例如人类白细胞抗原（HLA）-G，一种非经典的主要组织相容性复合物（MHC）I 类分子，通过与主要免疫效应细胞上存在的抑制性受体相互作用诱导耐受。最近，调节 MSC 介导的免疫抑制的分子机制受到了研究。我们的目标是确定 HLA-G 是否在免疫抑制中发挥关键作用，以及人脂肪组织（hAT）MSC 是否可以用作 HLA-G 在移植中生物免疫抑制的工具。
通过荧光激活细胞分选（FACS）分析、逆转录（RT）-聚合酶链反应（PCR）和分化染色来鉴定 MSC。通过外周血单核细胞（PBMC）增殖测定（有无植物血凝素（PHA）刺激）监测 MSC 的免疫原性和免疫调节作用。使用慢病毒系统实现 MSC 中 HLA-G1 的稳定表达。结果。不同组织来源的 MSC 具有相似的形态、免疫表型特征和分化潜能。我们还发现，MSC 的免疫抑制作用与内源性 HLA-G mRNA 和蛋白水平相关。HLA-G1 的稳定表达似乎增强了 hAT MSC 的免疫抑制作用，并且 HLA-G 拮抗抗体在 PBMC 增殖测定中显著降低了 HLA-G1 的功能。
尽管 HLA-G 分子不是 MSC 介导的免疫抑制的唯一因素，但我们的数据提供了证据表明 HLA-G 在免疫抑制中发挥重要作用，并且 hAT MSC 可以用作移植过程中生物免疫抑制的工具。
