Expression patterns of regulatory T-cell markers in accepted and rejected nonhuman primate kidney allografts

Expression patterns of regulatory T-cell markers in accepted and rejected nonhuman primate kidney allografts
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DOI:
10.1111/j.1600-6143.2007.01917.x
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发表时间:
2007-10-01
影响因子:
8.8
通讯作者:
Jonker, M.
Jonker, M.
中科院分区:
医学2区
文献类型:
--
作者:
Haanstra, K. G.;Wubben, J. A. M.;Jonker, M.

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在同种异体移植物的受体中,特别是在移植物本身内,识别FOXP 3表达细胞可能有助于定义免疫抑制药物撤药的标准。因此,我们检测了几种调节性T细胞(Treg)标志物在肾活检和肾组织中的表达模式,这些肾活检和肾组织是在接受α CD 40、α CD 86、CsA、这些治疗的组合或停药后采集的。在排斥的晚期,可以发现有组织的多灶性结节浸润,成熟的树突状细胞、T细胞和B细胞。相反,间质浸润中巨噬细胞较多,T细胞较少,B细胞较少,FOXP 3、CD 25和CTLA-4阳性细胞主要见于排斥组织结节性浸润。FOXP 3(+)细胞百分比与排斥反应标志物(即肌酐水平和Banff间质和肾小管浸润评分)之间存在显著相关性。免疫抑制的类型不影响表达Treg标志物的细胞的百分比。3只无药物存活时间延长的动物显示FOXP 3(+)细胞数量较少,我们的结论是,移植物内FOXP 3(+)细胞的存在并不局限于耐受的移植物,而应被认为是排斥反应中正常免疫反应的一部分。
The identification of FOXP3 expressing cells in recipients of an allograft, in particular inside the graft itself, may help to define criteria for immunosuppressive drug withdrawal. We therefore examined expression patterns of several regulatory T-cell (Treg) markers in kidney biopsies and kidney tissues taken at the time of graft rejection from monkeys treated with alpha CD40, alpha CD86, CsA, a combination of these or after drug withdrawal.In advanced stages of rejection, organized multifocal nodular infiltrates, with mature dendritic cells, T cells and B cells could be found. In contrast, interstitial infiltrates contain more macrophages, less T cells and few B cells.Cells expressing FOXP3, CD25 and CTLA-4 were mainly found in nodular infiltrates of rejected tissue samples. A significant correlation was found between the percentage FOXP3(+) cells and markers for rejection, i.e. creatinine levels and Banff interstitial and tubular infiltrate scores. The type of immunosuppression did not influence the percentage of cells expressing Treg markers. Three animals with prolonged drug-free survival showed low numbers of FOXP3(+) cells.We conclude that the presence of intragraft FOXP3(+) cells is not confined to tolerated grafts, but should be considered as part of the normal immune response during rejection.