Immunosuppressive effects of mesenchymal stem cells:: Involvement of HLA-G
Immunosuppressive effects of mesenchymal stem cells:: Involvement of HLA-G
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DOI：
10.1097/01.tp.0000267918.07906.08
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发表时间：
2007-07-27
期刊：
影响因子：
6.2
通讯作者：
Fouillard, Loic
中科院分区：
文献类型：
--
作者：
Nasef, Aisha;Mathieu, Noelle;Fouillard, Loic
介绍。间充质干细胞（MSCs）具有独特的免疫调节特性。它们能够抑制同种异体t细胞反应并修饰抗原呈递细胞的成熟。它们在治疗严重移植物抗宿主病中的作用已被报道。免疫抑制的潜在分子机制目前正在研究中。组织相容性位点抗原(HLA)-G是一种非经典的主要组织相容性复合体I类抗原，具有很强的免疫抑制特性。我们研究了HLA-G在msc诱导的免疫抑制中的作用。分析HLA-G在人骨髓间充质干细胞单独培养和混合淋巴细胞反应（MSC/MLR）中的表达情况。我们发现HLA-G可以通过实时反相聚合酶链反应、免疫荧光、流式细胞术（52.4 +/- 3.6%）和酶联免疫吸附法（38.7 +/- 5.2 ng/mL）在MSCs上检测到。在MSC/MLR中，HLA-G蛋白的表达是组成性的，并且在同种异体淋巴细胞的刺激下水平不改变。在MSC/MLR中使用87G抗HLA-G阻断抗体分析MSCs表达的HLA-G蛋白的功能作用。我们发现阻断HLA-G分子可显著提高MSC/MLR淋巴细胞增殖（35.5%，P=0.01）。我们的发现提供了支持HLA-G参与MSCs免疫抑制特性的证据。这些结果强调了MSCs作为移植相关治疗候选药物的潜在应用。
Introduction. Mesenchymal stem cells (MSCs) possess unique immunomodulatory properties. They are able to suppress allogenic T-cell response and modify maturation of antigen-presenting cells. Their role in the treatment of severe graft versus host disease has been reported. The underlying molecular mechanisms of immunosuppression are currently being investigated. Histocompatibility locus antigen (HLA)-G is a nonclassical major histocompatibility complex class I antigen with strong immune-inhibitory properties.Methods. We studied the role of HLA-G on MSC-induced immunosuppression. The expression of HLA-G on human MSCs cultured alone and in mixed lymphocytes reaction (MSC/MLR) was analyzed.Results. We found that HLA-G can be detected on MSCs by real-time reverse-phase polymerase chain reaction, immunofluorescence, flow cytometry (52.4 +/- 3.6%), and enzyme-linked immunosorbent assay in the supernatant (38.7 +/- 5.2 ng/mL). HLA-G protein expression is constitutive and the level is not modified upon stimulation by allogenic lymphocytes in MSC/MLR. The functional role of HLA-G protein expressed by MSCs was analyzed using the 87G anti-HLA-G blocking antibody in a MSC/MLR. We found that blocking HLA-G molecule significantly raised lymphocyte proliferation in MSC/MLR (35.5%, P=0.01).Conclusion. Our findings provide evidences supporting involvement of HLA-G in the immunosuppressive properties of MSCs. These results emphasize the potential application of MSCs as a relevant therapeutic candidate in transplantation.