Department of Internal Medicine, Transplantation Laboratory/Nephrology, Erasmus University Medical Center, Rotterdam, The Netherlands.
Cell Transplant. 2013;22(1):41-54. doi: 10.3727/096368912X636984. Epub 2012 Apr 2.
Mesenchymal stem cells (MSCs) exhibit immunosuppressive capabilities, which have evoked interest in their application as cell therapy in transplant patients. So far it has been unclear whether allogeneic MSCs and host regulatory T-cells (Tregs) functionally influence each other. We investigated the interaction between both cell types using perirenal adipose tissue-derived MSCs (ASCs) from kidney donors and Tregs from blood bank donors or kidney recipients 6 months after transplantation. The immunomodulatory capacity of ASCs was not prejudiced by both Tregs from healthy donors and Tregs from graft recipients, indicating that ASCs were not targeted by the inhibitory effects of Tregs and vice versa. In addition, Tregs supported ASC function, as they did not alter the secretion of IFN-γ by immune cells and hence contributed to ASC activation and efficiency. ASCs exerted their suppressive role by expressing IDO, reducing levels of TNF-α, and by inducing the production of IL-10 in effector cells and Tregs. In conclusion, this study presents evidence that donor ASCs and acceptor Tregs do not impair each other's function and therefore encourages the use of MSC therapy for the prevention of graft rejection in solid organ transplantation.
间充质干细胞（MSCs）具有免疫抑制能力，这激发了人们将其作为细胞疗法应用于移植患者的兴趣。到目前为止，异体 MSCs 和宿主调节性 T 细胞（Tregs）是否能相互影响尚不清楚。我们使用来自肾供体的肾周脂肪组织衍生的间充质干细胞（ASCs）和来自血库供体或移植后 6 个月的肾受体的 Tregs 研究了这两种细胞类型之间的相互作用。来自健康供体的 Tregs 和来自移植物受体的 Tregs 均未损害 ASC 的免疫调节能力，这表明 ASC 不受 Tregs 抑制作用的影响，反之亦然。此外，Tregs 支持 ASC 功能，因为它们不会改变免疫细胞分泌 IFN-γ，从而有助于 ASC 的激活和效率。ASC 通过表达 IDO、降低 TNF-α 水平以及在效应细胞和 Tregs 中诱导 IL-10 的产生来发挥其抑制作用。总之，本研究提供了证据表明供体 ASC 和受体 Tregs 不会损害彼此的功能，因此鼓励将 MSC 治疗用于预防实体器官移植中的移植物排斥。
