High numbers of differentiated CD28null CD8+ T cells are associated with a lowered risk for late rejection and graft loss after kidney transplantation
High numbers of differentiated CD28null CD8+ T cells are associated with a lowered risk for late rejection and graft loss after kidney transplantation
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DOI：
10.1371/journal.pone.0228096
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发表时间：
2020-02-05
期刊：
影响因子：
3.7
通讯作者：
Litjens, Nicolle H. R.
中科院分区：
文献类型：
--
作者：
Betjes, Michiel G. H.;Litjens, Nicolle H. R.
BackgroundThe假说进行了测试，参数的一个老化的T细胞室与肾transplantation.Methodsrecipients在2007-2013年期间的肾移植后的晚期排斥反应的风险（N = 365）被包括在内。在移植前通过流式细胞术将T细胞表征为初始（CD 45 RO（-）CCR 7（+））、中枢记忆（CD 45 RO（+）CCR 7（+））、效应记忆（CD 45 RO（-）CCR 7（-））或终末分化的CD 8（+）Temra（CD 45 RO（-）/CCR 7（-）/CD 28（-））细胞。在202例受者中，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。以移植后6个月以上首次出现排斥反应的时间作为无排斥反应生存时间。胸腺输出量和T细胞端粒长度与晚期无排斥生存率无关。但在晚期排斥反应患者中，CD 8（+）Temra和CD 28 null CD 8（+）T细胞的百分比和绝对数量均显著降低。具体而言，在CD 28 null CD 8（+）T细胞百分比最高的三分位数中，5年和10年时晚期排斥反应的累积发生率仅为5%和8%，而在中到最低的三分位数中，晚期排斥反应的累积发生率为16%和20%（p = 0.002）。多变量比例风险分析显示，CD 28 null CD 8（+）T细胞的百分比和绝对数量与肾移植术后晚期排斥反应和排斥相关的移植物丢失显著相关。
BackgroundThe hypothesis was tested that parameters of an aged T-cell compartment associate with the risk for late rejection after kidney transplantation.MethodsRecipients 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.ResultsFifty 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.ConclusionHigh numbers of differentiated CD28null CD8(+) T cells decrease the risk for late rejection and rejection-related graft loss after kidney transplantation.