Comparison of Regulatory T Cells in Hemodialysis Patients and Healthy Controls: Implications for Cell Therapy in Transplantation
Comparison of Regulatory T Cells in Hemodialysis Patients and Healthy Controls: Implications for Cell Therapy in Transplantation
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DOI：
10.2215/cjn.12931212
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发表时间：
2013-07-31
影响因子：
9.8
通讯作者：
Lombardi, Giovanna
中科院分区：
文献类型：
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作者：
Afzali, Behdad;Edozie, Francis C.;Lombardi, Giovanna
背景与目的利用天然（CD 4（+）CD 25（hi）CD 127（lo））调节性T细胞诱导移植耐受的细胞治疗目前在技术上是可行的。然而，来自等待移植的血液透析患者的调节性T细胞可能在功能上/数量上有缺陷。人类调节性T细胞也是异质性的，一些能够转化为促炎性Th 17细胞。本研究探讨了来自血液透析患者的调节性T细胞对于基于细胞的治疗的适用性，为肾移植受者的第一次临床试验（ONE研究）做准备。设计、设置、参与者和测量招募了健康对照和年龄和性别匹配的血液透析患者，这些患者最近没有疾病/自身免疫性疾病，并且接受了至少6个月的无并发症血液透析。通过流式细胞术研究循环调节性T细胞以比较调节性T细胞亚群。调节性T细胞的抑制功能和可塑性（IL-17产生能力）进行了比较，在体外扩增前后，有和没有雷帕霉素，使用标准assessment.Results两组有相似的总调节性T细胞和亚群I和III。在每个亚群中，调节性T细胞表达类似水平的功能相关标志物CD 27、CD 39、HLA-DR和FOXP 3。与健康对照调节性T细胞相比，血液透析调节性T细胞的抑制性较低，扩增较差，并且在不存在雷帕霉素的情况下产生IL-17。然而，雷帕霉素有效地扩大了血液透析调节T细胞的功能和稳定的细胞product.Conclusions雷帕霉素为基础的扩展协议，使临床试验的细胞为基础的免疫疗法的诱导肾移植耐受使用血液透析调节T细胞。
Background and objectives Cell-based therapy with natural (CD4(+)CD25(hi)CD127(lo)) regulatory T cells to induce transplant tolerance is now technically feasible. However, regulatory T cells from hemodialysis patients awaiting transplantation may be functionally/numerically defective. Human regulatory T cells are also heterogeneous, and some are able to convert to proinflammatory Th17 cells. This study addresses the suitability of regulatory T cells from hemodialysis patients for cell-based therapy in preparation for the first clinical trials in renal transplant recipients (the ONE Study).Design, setting, participants, & measurements Healthy controls and age- and sex-matched hemodialysis patients without recent illness/autoimmune disease on established, complication-free hemodialysis for a minimum of 6 months were recruited. Circulating regulatory T cells were studied by flow cytometry to compare the regulatory T cell subpopulations. Regulatory T cells from members of each group were compared for suppressive function and plasticity (IL-17-producing capacity) before and after in vitro expansion with and without Rapamycin, using standard assays.Results Both groups had similar total regulatory T cells and subpopulations I and III. In each subpopulation, regulatory T cells expressed similar levels of the function-associated markers CD27, CD39, HLA-DR, and FOXP3. Hemodialysis regulatory T cells were less suppressive, expanded poorly compared with healthy control regulatory T cells, and produced IL-17 in the absence of Rapamycin. However, Rapamycin efficiently expanded hemodialysis regulatory T cells to a functional and stable cell product.Conclusions Rapamycin-based expansion protocols should enable clinical trials of cell-based immunotherapy for the induction of tolerance to renal allografts using hemodialysis regulatory T cells.