Department of Internal Medicine, section Nephrology and Transplantation, Erasmus MC, University Medical Centre, Rotterdam, the Netherlands.
PLoS One. 2020 Feb 5;15(2):e0228096. doi: 10.1371/journal.pone.0228096. eCollection 2020.
The hypothesis was tested that parameters of an aged T-cell compartment associate with the risk for late rejection after kidney transplantation.
Recipients of a kidney transplant in the period 2007-2013 were (N = 365) were included. T cells were characterized prior to transplantation by flow cytometry as naive (CD45RO-CCR7+), central-memory (CD45RO+CCR7+), effector-memory (CD45RO-CCR7-) or terminally differentiated CD8+ Temra (CD45RO-/CCR7-/CD28-) cells. T cell telomere length and thymic output were assessed prior to transplantation in 202 recipients. Follow-up was until December 2018. The date of the first time of biopsy-proven late rejection (>6 months after transplantation) was used to calculate the rejection-free survival time.
Fifty cases of biopsy-proven rejection were recorded. Thymic output and T cell telomere length did not associate with late rejection-free survival. However, the percentage and absolute numbers of CD8+Temra and CD28null CD8+ T cells were significantly lower in patients with late rejection. Specifically, in the highest tertile of percentages of CD28null CD8+ T cells, the cumulative incidence of late rejection at 5 and 10 years was only 5% and 8% compared to 16% and 20% in the middle to lowest tertile (p = 0.002). Multivariate proportional hazard analysis showed that percentage and absolute number of CD28null CD8+ T cells remained significantly associated with late rejection and rejection-related graft loss.
High numbers of differentiated CD28null CD8+ T cells decrease the risk for late rejection and rejection-related graft loss after kidney transplantation.
本研究假设，衰老 T 细胞群体的参数与肾移植后晚期排斥反应的风险相关。
纳入 2007 年至 2013 年期间接受肾移植的患者（N=365）。在移植前通过流式细胞术对 T 细胞进行特征分析，分为幼稚（CD45RO-CCR7+）、中央记忆（CD45RO+CCR7+）、效应记忆（CD45RO-CCR7-）或终末分化的 CD8+ Temra（CD45RO-/CCR7-/CD28-）细胞。在 202 例患者中，在移植前评估 T 细胞端粒长度和胸腺输出。随访至 2018 年 12 月。将首次活检证实的晚期排斥（移植后>6 个月）的时间用于计算无排斥反应的生存时间。
记录了 50 例活检证实的排斥病例。胸腺输出和 T 细胞端粒长度与晚期无排斥反应的生存时间无关。然而，晚期排斥患者的 CD8+Temra 和 CD28null CD8+T 细胞的百分比和绝对数量明显较低。具体而言，在 CD28null CD8+T 细胞百分比最高的三分位组中，5 年和 10 年时的晚期排斥累积发生率仅为 5%和 8%，而中至最低三分位组分别为 16%和 20%（p=0.002）。多变量比例风险分析表明，CD28null CD8+T 细胞的百分比和绝对数量与晚期排斥和与排斥相关的移植物丢失仍然显著相关。
分化的 CD28null CD8+T 细胞数量高可降低肾移植后晚期排斥和与排斥相关的移植物丢失的风险。
