Institute of Biomedicine, Department of Anatomy and Cell Biology, University of Oulu, Oulu, Finland.
PLoS One. 2012;7(2):e31671. doi: 10.1371/journal.pone.0031671. Epub 2012 Feb 20.
Human mesenchymal stem cells (hMSCs) display immunosuppressive properties in vitro and the potential has also been transferred successfully to clinical trials for treatment of autoimmune diseases. OX-2 (CD200), a member of the immunoglobulin superfamily, is widely expressed in several tissues and has recently been found from hMSCs. The CD200 receptor (CD200R) occurs only in myeloid-lineage cells. The CD200-CD200R is involved in down-regulation of several immune cells, especially macrophages. The present study on 20 hMSC lines shows that the CD200 expression pattern varied from high (CD200Hi) to medium (CD200Me) and low (CD200Lo) in bone marrow-derived mesenchymal stem cell (BMMSC) lines, whereas umbilical cord blood derived mesenchymal stem cells (UCBMSCs) were constantly negative for CD200. The role of the CD200-CD200R axis in BMMSCs mediated immunosuppression was studied using THP-1 human macrophages. Interestingly, hMSCs showed greater inhibition of TNF-α secretion in co-cultures with IFN-γ primed THP-1 macrophages when compared to LPS activated cells. The ability of CD200Hi BMMSCs to suppress TNF-α secretion from IFN-γ stimulated THP-1 macrophages was significantly greater when compared to CD200Lo whereas UCBMSCs did not significantly reduce TNF-α secretion. The interference of CD200 binding to the CD200R by anti-CD200 antibody weakened the capability of BMMSCs to inhibit TNF-α secretion from IFN-γ activated THP-1 macrophages. This study clearly demonstrated that the efficiency of BMMSCs to suppress TNF-α secretion of THP-1 macrophages was dependent on the type of stimulus. Moreover, the CD200-CD200r axis could have a previously unidentified role in the BMMSC mediated immunosuppression.
人骨髓间充质干细胞（hMSCs）在体外具有免疫抑制特性，并且这种特性已经成功地转移到自身免疫性疾病的临床试验中。OX-2（CD200）是免疫球蛋白超家族的成员，广泛表达于几种组织中，最近在 hMSCs 中发现。CD200 受体（CD200R）仅出现在髓系细胞中。CD200-CD200R 参与了几种免疫细胞，特别是巨噬细胞的下调。本研究对 20 种 hMSC 系进行了研究，结果表明 CD200 的表达模式在骨髓间充质干细胞（BMMSC）系中从高（CD200Hi）到中（CD200Me）和低（CD200Lo）不等，而脐带血来源的间充质干细胞（UCBMSCs）则始终为 CD200 阴性。使用 THP-1 人巨噬细胞研究了 CD200-CD200R 轴在 BMMSCs 介导的免疫抑制中的作用。有趣的是，与 LPS 激活的细胞相比，在与 IFN-γ 预刺激的 THP-1 巨噬细胞共培养时，hMSCs 显示出对 TNF-α 分泌的更强抑制作用。与 CD200Lo 相比，CD200Hi BMMSCs 抑制 IFN-γ 刺激的 THP-1 巨噬细胞 TNF-α 分泌的能力显著增强，而 UCBMSCs 则没有显著降低 TNF-α 分泌。抗 CD200 抗体干扰 CD200 与 CD200R 的结合，削弱了 BMMSCs 抑制 IFN-γ 激活的 THP-1 巨噬细胞 TNF-α 分泌的能力。本研究清楚地表明，BMMSCs 抑制 THP-1 巨噬细胞 TNF-α 分泌的效率取决于刺激的类型。此外，CD200-CD200r 轴可能在 BMMSC 介导的免疫抑制中具有以前未被识别的作用。
