Impact of immunosuppressive drugs on circulating Tfh cells in kidney transplant recipients: A pilot study
Impact of immunosuppressive drugs on circulating Tfh cells in kidney transplant recipients: A pilot study
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免疫抑制药物对肾移植受者循环 Tfh 细胞的影响：一项试点研究。
DOI：
10.1016/j.trim.2017.09.005
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发表时间：
2018-02-01
影响因子：
1.5
通讯作者：
Wang, Lan Lan
中科院分区：
文献类型：
--
作者：
Li, Ya Mei;Li, Yi;Wang, Lan Lan
背景：最近发现T滤泡辅助细胞(TFH)在肾移植受者抗体介导的排斥反应(AMR)中起重要作用。然而，免疫抑制药物对TFH细胞的影响尚不完全清楚。本研究的目的是研究不同免疫抑制方案对KTRs表型和功能的影响。方法：26例KTRs接受他克莫司(TAC)方案治疗，13例接受西罗莫司(SRL)方案治疗，10例健康对照(HC)。结果：TAC组TFH细胞百分率、绝对数及PD-1、STAT3共表达均显著高于SRL组，TFH细胞百分率、绝对数及TFH相关分子共表达水平均显著高于SRL组。而IL-21和ICOS与TFH细胞共表达的情况在三组间无差异。多元线性回归分析结果显示，移植前PRA水平是影响TfH和CD4+CXCR5+PD-1+T细胞绝对数的显著混杂因素。相关分析显示，CD4+CXCR5+STAT3+T细胞与TTH细胞呈正相关。结论：西罗莫司对TFH细胞数量的抑制作用优于他克莫司。他克莫司组外周血中Tfh细胞水平升高可能与STAT3信号转导有关。
Background: T follicular helper cells (Tfh) are recently revealed to be vital in antibody-mediated rejection (AMR) in kidney transplant recipients (KTRs). However, the impact of immunosuppressive drugs on Tfh cells is not fully understood. The purpose of this study was to investigate the variation of Tfh cells phenotypically and functionally in KTRs treated with different immunosuppression regimens.Methods: We recruited 26 KTRs treated with tacrolimus (TAC)-based regimen, 13 with sirolimus (SRL)-based regimen and 10 healthy controls (HC) in this study. The percentage and absolute number of circulating Tfh cells and the co-expression of Tfh related molecules including inducible costimulatory molecule (ICOS), programmed cell death protein 1 (PD-1), interleukin-21 (IL-21) and signal transducer and activator of transcription 3 (STAT3) were analyzed by flow cytometry, while serum IL-6 was detected by electrochemiluminescence immunoassay.Results: The percentage and absolute number of Tfh cells and the co-expression of PD-1, STAT3 in Tfh cells were significantly higher in TAC group than that in SRL group. While no difference was found in regard to IL-21 and ICOS co-expressed with Tfh cells among three groups. Multiple linear regression analysis results showed that pre-transplant PRA level was the significant confounder affecting the absolute numbers of Tfh and CD4 + CXCR5 + PD-1 + T cells. In addition, correlation analysis showed that CD4 + CXCR5 + STAT3 + T cells were positively correlated to Tth cells.Conclusions: Our study indicates that sirolimus can suppress the quantity of Tfh cells more significantly than tacrolimus. The higher level of circulating Tfh cells in tacrolimus group might be related to STAT3 signaling.