移植前受者循环CD4+CD127lo/-肿瘤坏死因子受体2+调节性T细胞：调节性T细胞抑制功能的替代指标及肾移植后移植肾功能延迟和缓慢的预测指标

Pretransplant Recipient Circulating CD4+CD127lo/- Tumor Necrosis Factor Receptor 2+ Regulatory T Cells: A Surrogate of Regulatory T Cell-Suppressive Function and Predictor of Delayed and Slow Graft Function After Kidney Transplantation.

作者信息

Nguyen Minh-Tri J P, Fryml Elise, Sahakian Sossy K, Liu Shuqing, Cantarovich Marcelo, Lipman Mark, Tchervenkov Jean I, Paraskevas Steven

机构信息

1 Multi-Organ Transplant Program, McGill University Health Centre, McGill University, Montreal, QC, Canada. 2 Division of General Surgery, Department of Surgery, McGill University Health Centre, McGill University, Montreal, QC, Canada. 3 Division of Nephrology, Department of Medicine, McGill University Health Centre, McGill University, Montreal, QC, Canada. 4 Division of Nephrology, Department of Medicine, Jewish General Hospital, McGill University, Montreal, QC, Canada.

出版信息

Transplantation. 2016 Feb;100(2):314-24. doi: 10.1097/TP.0000000000000942.

DOI:10.1097/TP.0000000000000942

PMID:26425877

Abstract

BACKGROUND

Delayed graft function (DGF) and slow graft function (SGF) are ischemia-reperfusion-associated acute kidney injuries (AKI) that decrease long-term graft survival after kidney transplantation. Regulatory T (Treg) cells are protective in murine AKI, and their suppressive function predictive of AKI in kidney transplantation. The conventional Treg cell function coculture assay is however time-consuming and labor intensive. We sought a simpler alternative to measure Treg cell function and predict AKI.

METHODS

In this prospective observational cohort study, pretransplant recipient circulating CD4+CD25+CD127lo/- and CD4+CD127lo/- tumor necrosis factor receptor 2 (TNFR2)+ Treg cells were measured by flow cytometry in 76 deceased donor kidney transplant recipients (DGF, n = 18; SGF, n = 34; immediate graft function [IGF], n = 24). In a subset of 37 recipients, pretransplant circulating Treg cell-suppressive function was also quantified by measuring the suppression of autologous effector T-cell proliferation by Treg cell in coculture.

RESULTS

The TNFR2+ expression on CD4+CD127lo/- T cells correlated with Treg cell-suppressive function (r = 0.63, P < 0.01). In receiver operating characteristic curves, percentage and absolute number of CD4+CD127lo/-TNFR2+ Treg cell predicted DGF from non-DGF (IGF + SGF) with area under the curves of 0.75 and 0.77, respectively, and also AKI (DGF + SGF) from IGF with area under the curves of 0.76 and 0.72, respectively (P < 0.01). Prediction of AKI (DGF + SGF) from IGF remained significant in multivariate logistic regression accounting for cold ischemic time, donor age, previous transplant, and pretransplant dialysis modality.

CONCLUSIONS

Pretransplant recipient circulating CD4+CD127lo/-TNFR2+ Treg cell is potentially a simpler alternative to Treg cell function as a pretransplant recipient immune marker for AKI (DGF + SGF), independent from donor and organ procurement characteristics.

摘要

背景

移植肾功能延迟恢复（DGF）和移植肾功能缓慢恢复（SGF）是与缺血再灌注相关的急性肾损伤（AKI），会降低肾移植后的长期移植肾存活率。调节性T（Treg）细胞在小鼠急性肾损伤中具有保护作用，其抑制功能可预测肾移植中的急性肾损伤。然而，传统的Treg细胞功能共培养检测方法耗时且费力。我们寻求一种更简单的方法来测量Treg细胞功能并预测急性肾损伤。

方法

在这项前瞻性观察队列研究中，通过流式细胞术检测了76例已故供体肾移植受者（DGF，n = 18；SGF，n = 34；即刻移植肾功能[IGF]，n = 24）移植前受者循环中的CD4+CD25+CD127lo/-和CD4+CD127lo/-肿瘤坏死因子受体2（TNFR2）+ Treg细胞。在37例受者的亚组中，还通过测量共培养中Treg细胞对自体效应T细胞增殖的抑制作用来量化移植前循环Treg细胞的抑制功能。

结果

CD4+CD127lo/- T细胞上的TNFR2+表达与Treg细胞抑制功能相关（r = 0.63，P < 0.01）。在受试者工作特征曲线中，CD4+CD127lo/-TNFR2+ Treg细胞的百分比和绝对数量预测DGF与非DGF（IGF + SGF），曲线下面积分别为0.75和0.77，预测AKI（DGF + SGF）与IGF，曲线下面积分别为0.76和0.72（P < 0.01）。在多因素逻辑回归中，考虑冷缺血时间、供体年龄、既往移植和移植前透析方式后，从IGF预测AKI（DGF + SGF）仍然具有显著性。