Human mesenchymal stem cells alter antigen-presenting cell maturation and induce T-cell unresponsiveness
Human mesenchymal stem cells alter antigen-presenting cell maturation and induce T-cell unresponsiveness
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DOI：
10.1182/blood-2004-07-2921
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发表时间：
2005-03-01
期刊：
影响因子：
20.3
通讯作者：
Rachmilewitz, J
中科院分区：
文献类型：
--
作者：
Beyth, S;Borovsky, Z;Rachmilewitz, J
胚胎干细胞或间充质干细胞的输注提高了来源于干细胞供体的器官移植物的存活率，并预防了移植物抗宿主病（GVHD）。对这种耐受现象的深入机制理解可能会导致新的基于细胞的移植疗法。在这里，我们证明，虽然人间充质干细胞（hMSC）可以促进超抗原诱导的纯化T细胞活化，但向培养物中添加抗原递呈细胞（APC;单核细胞或树突状细胞）会抑制T细胞反应。这种接触和剂量依赖性抑制伴随着大量白细胞介素（IL）-10的分泌和异常APC成熟，这可以通过添加促进APC成熟的因子（即脂多糖[LPS]或抗CD 40单克隆抗体[mAb]）部分抵消。因此，我们的数据支持的免疫调节机制，其中hMSC抑制T细胞间接的接触依赖性诱导的调节APCs与T细胞抑制性能。我们的数据可能揭示了一种生理现象，即一个独特的APC群体的发展是由组织的细胞微环境调节。(C)2005年美国血液学会
infusion of either embryonic or mesenchymal stem cells prolongs the survival of organ transplants derived from stem cell donors and prevents graft-versus-host-disease (GVHD). An in-depth mechanistic understanding of this tolerization phenomenon could lead to novel cell-based therapies for transplantation. Here we demonstrate that while human mesenchymal stem cells (hMSCs) can promote superantigen-induced activation of purified T cells, addition of antigen-presenting cells (APCs; either monocytes or dendritic cells) to the cultures inhibits the T-cell responses. This contact- and dose-dependent inhibition is accompanied by secretion of large quantities of interleukin (IL)-10 and aberrant APC maturation, which can be partially overridden by the addition of factors that promote APC maturation (ie, lipopolysaccharide [LPS] or anti-CD40 monoclonal antibody [mAb]). Thus, our data support an immunoregulatory mechanism wherein hMSCs inhibit T cells indirectly by contact-dependent induction of regulatory APcs with T-cell-suppressive properties. Our data may reveal a physiologic phenomenon whereby the development of a distinct APC population is regulated by the tissue's cellular microenvironment. (C) 2005 by The American Society of Hematology