首页> 外文期刊>The journal of immunology >Immunomodulation of Delayed-Type Hypersensitivity Responses by Mesenchymal Stem Cells Is Associated with Bystander T Cell Apoptosis in the Draining Lymph Node
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Immunomodulation of Delayed-Type Hypersensitivity Responses by Mesenchymal Stem Cells Is Associated with Bystander T Cell Apoptosis in the Draining Lymph Node

机译:间充质干细胞延迟型超敏反应的免疫调节与引流淋巴结中的旁观者T细胞凋亡有关。

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Disease amelioration by mesenchymal stem cells (MSCs) has been shown to be closely related to their immunomodulatory functions on the host immune system in many disease models. However, the underlying mechanisms of how these cells affect the immune cells in vivo are not fully understood. In this study, we report findings that a small but significant number of MSCs accumulate in the secondary lymphoid organs and attenuate delayed-type hypersensitivity (DTH) response by inducing apoptotic cell death of surrounding immune cells in the draining lymph node (LN). In the migration study, i.v. infused GFP-MSCs preferentially accumulated at the boundary between the paracortical area and the germinal center in the LNs, in close proximity to various types of immune cells including T, B, and dendritic cells in a dose-dependent manner. As a result, accumulated MSCs markedly attenuated DTH response in proportion to the number of MSCs infused. During the DTH response, the infiltration of T cells in the challenged site was significantly decreased, whereas a number of apoptotic T cells were remarkably increased in the draining LN. Apoptosis was significantly induced in activated T cells (CD3+ and BrdU+), but not in the resting T cells (CD3+ and BrdU?). NO was associated with these apoptotic events. Taken together, we conclude that significant numbers of i.v. infused MSCs preferentially localize in the draining LN, where they induce apoptosis of the activated T cells by producing NO and thus attenuate the DTH response.
机译:在许多疾病模型中,间充质干细胞(MSC)的疾病改善与它们对宿主免疫系统的免疫调节功能密切相关。但是,这些细胞如何影响体内免疫细胞的潜在机制尚未完全了解。在这项研究中,我们报告发现,少量但大量的MSC在次级淋巴器官中蓄积,并通过在引流淋巴结(LN)中诱导周围免疫细胞的凋亡而死亡,从而减弱了迟发型超敏反应(DTH)的反应。在迁移研究中,注入的GFP-MSC优先以剂量依赖的方式积聚在LNs的皮层旁区域和生发中心之间的边界处,并紧邻各种类型的免疫细胞,包括T,B和树突状细胞。结果,累积的MSC与注入的MSC数量成比例地显着减弱了DTH反应。在DTH反应期间,受攻击部位的T细胞浸润明显减少,而引流LN中凋亡T细胞的数量显着增加。在活化的T细胞(CD3 +和BrdU +)中明显诱导了细胞凋亡,而在静止的T细胞(CD3 +和BrdU2)中没有诱导凋亡。 NO与这些凋亡事件有关。综上所述,我们得出结论,大量i.v.注入的MSC优先定位在引流的LN中,在那里它们通过产生NO诱导激活的T细胞凋亡,从而减弱DTH反应。

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