DR(high+)CD45RA(-)-Tregs potentially affect the suppressive activity of the total Treg pool in renal transplant patients.

DR(high+)CD45RA(-)-Tregs potentially affect the suppressive activity of the total Treg pool in renal transplant patients.
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DOI:
10.1371/journal.pone.0034208
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发表时间:
2012
期刊:
影响因子:
3.7
通讯作者:
Steinborn A
Steinborn A
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Schaier M;Seissler N;Schmitt E;Meuer S;Hug F;Zeier M;Steinborn A

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近年来的研究表明,调节性T细胞(regulatory T cells, Tregs)在器官移植后的耐受诱导中起着至关重要的作用。为了研究稳定移植患者和活检证实排斥(BPR)患者的总CD4+CD127low+/−FoxP3+- Treg细胞池的组成是否存在差异,我们比较了不同Treg细胞亚群(DRhigh+CD45RA−- tregs, DRlow+CD45RA−- tregs, DR - CD45RA−- tregs, DR - CD45RA+- tregs)的百分比和功能活性。在移植后的3个不同时期(0-30天、31 - 1000天、10 - 1000天)测定所有参数。156例移植患者中,37例发生BPR。排斥和非排斥患者之间最显著的差异是DRhigh+CD45RA−-Treg细胞亚群。我们的数据表明,整个Treg池的抑制活性强烈依赖于这些Treg细胞的存在。它们在移植后总Treg池中的百分比急剧下降,并且在所有患者移植后的第一年保持相对较低。随后,在接受移植的患者中,该Treg亚群的比例再次增加,并达到健康非移植受试者的值。相比之下,在急性肾排斥患者中,DRhigh+CD45RA−-Treg亚群过度消失,导致Treg总库抑制活性降低。因此,监测其在总Treg池中的百分比和监测DR+CD45RA−-Treg亚群的HLA-DR MFI可能是预测移植物排斥反应的有用工具。
Recent studies show that regulatory T cells (Tregs) play an essential role in tolerance induction after organ transplantation. In order to examine whether there are differences in the composition of the total CD4+CD127low+/−FoxP3+- Treg cell pool between stable transplant patients and patients with biopsy proven rejection (BPR), we compared the percentages and the functional activity of the different Treg cell subsets (DRhigh+CD45RA−-Tregs, DRlow+CD45RA−-Tregs, DR−CD45RA−-Tregs, DR−CD45RA+-Tregs). All parameters were determined during the three different periods of time after transplantation (0–30 days, 31–1,000 days, >1,000 days). Among 156 transplant patients, 37 patients suffered from BPR. The most prominent differences between rejecting and non-rejecting patients were observed regarding the DRhigh+CD45RA−-Treg cell subset. Our data demonstrate that the suppressive activity of the total Treg pool strongly depends on the presence of these Treg cells. Their percentage within the total Treg pool strongly decreased after transplantation and remained relatively low during the first year after transplantation in all patients. Subsequently, the proportion of this Treg subset increased again in patients who accepted the transplant and reached a value of healthy non-transplanted subjects. By contrast, in patients with acute kidney rejection, the DRhigh+CD45RA−-Treg subset disappeared excessively, causing a reduction in the suppressive activity of the total Treg pool. Therefore, both the monitoring of its percentage within the total Treg pool and the monitoring of the HLA-DR MFI of the DR+CD45RA−-Treg subset may be useful tools for the prediction of graft rejection.
CD127表达与FOXP3和人类CD4+ T Reg细胞的抑制功能成反比。
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