Li Ya Mei, Li Yi, Shi Yun Ying, Yan Lin, Wu Xiao Juan, Tang Jiang Tao, Bai Yang Juan, Wang Lan Lan
Department of Laboratory Medicine/Research Centre of Clinical Laboratory Medicine, West China Hospital, Sichuan University, Chengdu, China.
Department of Nephrology, West China Hospital, Sichuan University, Chengdu, China.
Transpl Immunol. 2018 Feb;46:1-7. doi: 10.1016/j.trim.2017.09.005. Epub 2017 Sep 30.
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.
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.
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 Tfh cells.
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.
滤泡辅助性T细胞（Tfh）最近被发现对肾移植受者（KTRs）的抗体介导排斥反应（AMR）至关重要。然而，免疫抑制药物对Tfh细胞的影响尚未完全明确。本研究的目的是调查接受不同免疫抑制方案治疗的KTRs中Tfh细胞在表型和功能上的变化。
本研究招募了26例接受基于他克莫司（TAC）方案治疗的KTRs、13例接受基于西罗莫司（SRL）方案治疗的KTRs以及10名健康对照者（HC）。通过流式细胞术分析循环Tfh细胞的百分比和绝对数量以及Tfh相关分子的共表达情况，这些分子包括诱导性共刺激分子（ICOS）、程序性细胞死亡蛋白1（PD-1）、白细胞介素-21（IL-21）和信号转导及转录激活因子3（STAT3），同时采用电化学发光免疫分析法检测血清IL-6。
TAC组Tfh细胞的百分比、绝对数量以及Tfh细胞中PD-1、STAT3的共表达均显著高于SRL组。而三组中与Tfh细胞共表达的IL-21和ICOS未发现差异。多元线性回归分析结果显示，移植前群体反应性抗体（PRA）水平是影响Tfh和CD4+CXCR5+PD-1+ T细胞绝对数量的显著混杂因素。此外，相关性分析表明CD4+CXCR5+STAT3+ T细胞与Tfh细胞呈正相关。
我们的研究表明，西罗莫司比他克莫司更能显著抑制Tfh细胞的数量。他克莫司组循环Tfh细胞水平较高可能与STAT3信号传导有关。
