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主题:干扰素γ在人骨髓间充质干细胞免疫调制活性中的作用
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说明:原文来自Stem Cells,干细胞之家新闻小组成员deron翻译(转帖请注明)! v& L: x+ Z4 l: u% |
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翻译内容:3 ~* U' _4 ~; i6 Z" A, y# f3 {( k
间充质干细胞(MSCs)抑制同种异基因抗原刺激中HLA非相关T淋巴细胞的增殖,但是这种活性的作用机制尚未探明。本文我们证明了MSCs能够抑制CD4+CD8+T淋巴细胞和自然杀伤性(NK)细胞的增值,然而其对B淋巴细胞增值无作用。MSCs的抑制效应与细胞活性标记表达、细胞凋亡诱导及T调节细胞活性模拟/增强没有任何关联。MSCs的抑制活性无接触依赖性,且需要活化T细胞和NK细胞产生的IFNγ的参与。相应的,在外源性IFNγ存在的前提下,MSCs甚至可以抑制活化的B细胞。IFNγ的抑制作用体现在其可以刺激MSCs生成吲哚胺2,3二氧化酶,后者可以依次抑制活化T细胞或NK细胞的增殖。这些发现表明:共注入的MSCs之所以在移植物抗宿主疾病中发挥积极作用,可能是因为T细胞来源的IFNγ激活了MSCs的免疫调节特性。
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原摘要:Mesenchymal stem cells (MSCs) inhibit the proliferation of HLA-unrelated T lymphocytes to allogeneic stimulation, but the mechanisms responsible for this activity are not fully understood. We show here that MSCs suppress the proliferation of both CD4+ and CD8+ T lymphocytes, as well as of natural killer (NK) cells, whereas they do not have an effect on the proliferation of B lymphocytes. The antiproliferative effect of MSCs was not associated with any effect on the expression of cell-activation markers, induction of cell apoptosis, or mimicry/enhancement of T regulatory cell activity. The suppressive activity of MSCs was not contact-dependent and required the presence of interferon (IFN)-gamma produced by activated T cells and NK cells. Accordingly, even activated B cells became susceptible to the suppressive activity of MSCs in the presence of exogenously added IFN-gamma. The suppressive effect of IFN-gamma was related to its ability to stimulate the production by MSCs of indoleamine 2,3-dioxygenase activity, which in turn inhibited the proliferation of activated T or NK cells. These findings suggest that the beneficial effect on graft-versus-host disease induced by in vivo coinfusion with the graft of MSCs may be due to the activation of the immunomodulatory properties of MSCs by T cell- derived IFN-gamma.) D5 G4 ?' ]# ^3 R( H( ~
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