Long-lasting inhibitory effects of fetal liver mesenchymal stem cells on T-lymphocyte proliferation.
Long-lasting inhibitory effects of fetal liver mesenchymal stem cells on T-lymphocyte proliferation.
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DOI：
10.1371/journal.pone.0019988
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发表时间：
2011
期刊：
影响因子：
3.7
通讯作者：
Durrbach A
中科院分区：
文献类型：
--
作者：
Giuliani M;Fleury M;Vernochet A;Ketroussi F;Clay D;Azzarone B;Lataillade JJ;Durrbach A
人骨髓间充质干细胞(BM-MSC)是一种对自然杀伤细胞(NK细胞)、树突状细胞(DC)和T细胞具有瞬时免疫调节作用的多能祖细胞。这项研究比较了从骨髓和胎肝分离的MSC(FL-MSC)的使用，以确定哪种方法对T细胞激活具有最有效的免疫抑制作用。虽然这两种类型的MSC表现出相似的表型特征，但FL-MSC在体外表现出更长的寿命和免疫调节特性。与CD3/CD28刺激的T细胞共培养时，BM-MSC和FL-MSC均通过抑制T细胞进入细胞周期，下调视网膜母细胞瘤(PRB)、细胞周期蛋白A和细胞周期蛋白D1的表达，上调p27kip1的表达，从而影响T细胞的增殖。MSC对T细胞的抑制不是由于可溶性的HLA-G5亚型，而是由于需要细胞间接触和使用中和的抗HLA-G抗体而使其表面表达了HLA-G1。值得注意的是，在人类白细胞抗原G介导的方式中，骨髓间充质干细胞促进了CD4low/CD8low T亚群的扩大，该亚群减少了干扰素-γ的分泌，并诱导了免疫调节细胞因子IL-10的分泌。胎肝间充质干细胞具有较长的体外免疫抑制特性，主要由人类白细胞抗原G介导，能更有效地诱导IL-10的产生和T细胞的凋亡，有望成为MSC治疗预防同种异体排斥反应的新工具。
Human bone marrow mesenchymal stem cells (BM-MSC) are multipotent progenitor cells that have transient immunomodulatory properties on Natural Killer (NK) cells, Dendritic Cells (DC), and T cells. This study compared the use of MSC isolated from bone marrow and fetal liver (FL-MSC) to determine which displayed the most efficient immunosuppressive effects on T cell activation. Although both types of MSC exhibit similar phenotype profile, FL-MSC displays a much more extended in vitro life-span and immunomodulatory properties. When co-cultured with CD3/CD28-stimulated T cells, both BM-MSC and FL-MSC affected T cell proliferation by inhibiting their entry into the cell cycle, by inducing the down-regulation of phospho-retinoblastoma (pRb), cyclins A and D1, as well as up-regulating p27kip1expression. The T cell inhibition by MSC was not due to the soluble HLA-G5 isoform, but to the surface expression of HLA-G1, as shown by the need of cell-cell contact and by the use of neutralizing anti-HLA-G antibodies. To note, in a HLA-G-mediated fashion, MSC facilitated the expansion of a CD4low/CD8low T subset that had decreased secretion of IFN-γ, and an induced secretion of the immunomodulatory cytokine IL-10. Because of their longer lasting in vitro immunosuppressive properties, mainly mediated by HLA-G, and their more efficient induction of IL-10 production and T cell apoptosis, fetal liver MSC could be considered a new tool for MSC therapy to prevent allograft rejection.
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影响因子：
6.2
作者：
Nasef, Aisha;Mathieu, Noelle;Fouillard, Loic
通讯作者：
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影响因子：
5.4
作者：
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通讯作者：
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5.2
作者：
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影响因子：
2.6
作者：
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通讯作者：
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影响因子：
20.3
作者：
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通讯作者：
Dilloo, D