Donor-specific alloreactive T cells can be quantified from whole blood, and may predict cellular rejection after renal transplantation
Donor-specific alloreactive T cells can be quantified from whole blood, and may predict cellular rejection after renal transplantation
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DOI：
10.1002/eji.201646826
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发表时间：
2017-07-01
影响因子：
5.4
通讯作者：
Sester, Urban
中科院分区：
文献类型：
--
作者：
Fischer, Michaela;Leyking, Sarah;Sester, Urban
移植前可能存在预先形成的细胞同种异体反应性，并可能导致排斥反应。在这里，我们使用了一种快速的流式细胞仪全血分析来表征来自61个肾移植候选者和75个对照组的1491个刺激反应中同种异体反应性T细胞的程度。前瞻性分析了21例肾移植受者预先形成的供体特异性同种异体反应性T细胞在细胞排斥反应中的作用。同种异体反应性CD8(+)T细胞比相应的CD4(+)T细胞更常见，而且这些水平随着时间的推移是稳定的。CD8(+)T细胞是主要表达CD27、CD62L和CCR7的记忆效应T细胞，对类固醇和钙调神经磷酸酶抑制剂敏感。同种异体反应性在人类白细胞抗原失配数量较多的样本中更为常见。此外，移植候选者中具有同种异体反应性T细胞的个体百分比高于对照组。在移植候选者中，5/61对大多数刺激物表现出同种异体反应的CD8(+)T细胞，23/61对有限的刺激物表现出同种异体反应，33/61没有表现出任何同种异体反应。在前瞻性随访的21例肾移植受者中，有一例出现供者特异性预形成T细胞同种异体反应。她是唯一一位移植后出现细胞排斥反应的患者。总之，供者特异性同种异体反应性T细胞可以从全血中快速定量，并可以预测移植后的细胞排斥反应。
Preformed cellular alloreactivity can exist prior to transplantation and may contribute to rejection. Here, we used a rapid flow-cytometric whole-blood assay to characterize the extent of alloreactive T cells among 1491 stimulatory reactions from 61 renal transplant candidates and 75 controls. The role of preformed donor-specific alloreactive T cells in cellular rejection was prospectively analyzed in 21 renal transplant recipients. Alloreactive CD8(+) T cells were more frequent than respective CD4(+) T cells, and these levels were stable over time. CD8(+) T cells were effector-memory T cells largely negative for expression of CD27, CD62L, and CCR7, and were susceptible to steroid and calcineurin inhibitor inhibition. Alloreactivity was more frequent in samples with higher number of HLA mismatches. Moreover, the percentage of individuals with alloreactive T cells was higher in transplant candidates than in controls. Among transplant candidates, 5/61 exhibited alloreactive CD8(+) T cells against most stimulators, 23/61 toward a limited number of stimulators, and 33/61 did not show any alloreactivity. Among 21 renal transplant recipients followed prospectively, one had donor-specific preformed T-cell alloreactivity. She was the only patient who developed cellular rejection posttransplantation. In conclusion, donor-specific alloreactive T cells may be rapidly quantified from whole blood, and may predict cellular rejection after transplantation.