Clinical Significance of Regulatory T-Cell-Related Gene Expression in Peripheral Blood After Renal Transplantation
Clinical Significance of Regulatory T-Cell-Related Gene Expression in Peripheral Blood After Renal Transplantation
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DOI：
10.1097/tp.0b013e3181ffbab4
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发表时间：
2011-01-27
期刊：
影响因子：
6.2
通讯作者：
Nakao, Akimasa
中科院分区：
文献类型：
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作者：
Iwase, Hayato;Kobayashi, Takaaki;Nakao, Akimasa
背景调节性T细胞（Regulatory T cells，Tcells）与移植免疫耐受和移植物长期存活密切相关。一些移植功能稳定（ST）的受体可能会在维持期尽量减少免疫抑制。然而，尚未建立用于评估患者适合性的有效测定法。本研究旨在探讨肾移植术后外周血Treg相关基因如叉头盒P3（Foxp 3）表达的临床意义。与免疫细胞功能相关的几种关键分子如Treg，包括Foxp 3、转化生长因子-β、细胞毒性T淋巴细胞抗原-4、趋化因子受体7、toll样受体4、颗粒酶B、T-bet、GATA 3、RORC、α（1，2）-甘露糖苷酶、和蛋白酶体亚单位β 10在272例肾移植受者的外周血中进行了检测，转录酶聚合酶链反应。比较慢性排斥反应和ST的表达水平。Foxp 3信使RNA（mRNA）水平在移植后立即降低并逐渐恢复。移植前水平与移植后1年水平密切相关。与ST组相比，慢性排斥组Foxp 3、趋化因子受体7和颗粒酶B mRNA水平显著降低，而Toll样受体4和蛋白酶体亚单位β 10 mRNA水平显著升高，尽管Foxp 3是最相关的标志物。监测外周血中Treg相关分子的mRNA表达水平可能为肾移植中实施免疫抑制最小化策略时的患者选择和排斥反应的早期检测提供有用的信息。
Background. Regulatory T cells (Tregs) have been suggested to be deeply associated with immune tolerance and long-term graft survival in transplantation. Some recipients with stable graft function (ST) could possibly minimize immunosuppression during the maintenance period. However, effective assays for assessing the suitability of patients have yet to be established. The purpose of this study was to elucidate the clinical relevance of Treg-related gene expression such as forkhead box P3 (Foxp3) in peripheral blood after renal transplantation.Methods. Several key molecules related to the function of immune cells such as Treg, including Foxp3, transforming growth factor-beta, cytotoxic T-lymphocyte antigen-4, chemokine receptor 7, toll-like receptor 4, granzyme B, T-bet, GATA3, RORC, alpha(1,2)-mannosidase, and proteasome subunit beta 10 were examined in the peripheral blood of 272 renal transplant recipients by quantitative real-time reverse-transcriptase polymerase chain reaction. The expression levels were compared between recipients with chronic rejection and ST.Results. Foxp3 messenger RNA (mRNA) levels were reduced immediately after transplantation and gradually recovered. Pretransplantation levels were closely correlated with 1 year posttransplantation levels. Recipients with chronic rejection had significantly lower levels of Foxp3, chemokine receptor 7, and granzyme B mRNA, and higher levels of toll-like receptor 4 and proteasome subunit beta 10 mRNA compared with those with ST, although Foxp3 was the most relevant marker.Conclusion. There is a possibility that monitoring mRNA expression levels of Treg-related molecules in peripheral blood might offer useful information on patient selection and early detection of rejection when immunosuppression minimization strategy is implemented in renal transplantation.