Calcineurin inhibitors, but not rapamycin, reduce percentages of CD4+CD25+FOXP3+ regulatory T cells in renal transplant recipients
Calcineurin inhibitors, but not rapamycin, reduce percentages of CD4+CD25+FOXP3+ regulatory T cells in renal transplant recipients
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DOI：
10.1097/01.tp.0000229473.95202.50
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发表时间：
2006-08-27
期刊：
影响因子：
6.2
通讯作者：
Arias, Manuel
中科院分区：
文献类型：
--
作者：
Segundo, David San;Ruiz, Juan Carlos;Arias, Manuel
背景资料。肾移植中的免疫抑制，虽然在短期内是可以处理的，但却是移植物长期存活的主要障碍。最近，CD4(+)CD25高调节性T细胞(Tregs)频率的增加被描述为诱导同种免疫耐受的另一种机制。我们对肾移植受者进行了至少一年的肾功能稳定评估。根据患者在研究期间接受的免疫抑制情况，患者被分为两组：一组接受雷帕霉素(RAPA)但不接受钙调神经磷酸酶抑制剂(CNI)，另一组接受CNI但不接受RAPA。根据他们以前使用CNI的经验，RAPA组进一步分为三个亚组：无CNI组、CNI停用组和CNI转换组。用抗Tregs不同标记物的单抗染色后，用流式细胞仪检测Tregs的频率。接受CNI治疗的肾移植患者外周血中具有调节表型和功能的CD4(+)T细胞的频率明显低于接受RAPA治疗的患者。这种影响与早期接触CNI无关，因为RAPA组中无CNI的患者表现出与CNI停用组和CNI转换组相似的Tregs频率。在稳定的肾移植受者中，CNI而不是RAPA诱导循环Tregs减少。因此，RAPA可能会在保存Tregs用于移植耐受的策略上进一步探索。此外，血树突状细胞的定量可能是确定肾移植受者可能是减少免疫抑制的候选对象的合适工具。
Background. Immunosuppression in renal transplantation, although manageable in the short-term, is a major hurdle for long-term graft survival. Recently, increased frequencies of CD4(+)CD25high regulatory T cells (Tregs) have been described as an additional mechanism that induces alloimmune tolerance.Methods. We assessed 64 renal transplant recipients with stable renal function for at least one year. Patients were divided into two groups according to the immunosuppression they were receiving at the moment of the study: one consisted of patients receiving rapamycin (Rapa) but not calcineurin inhibitors (CNI), and the other group received CNI but not Rapa. The Rapa group was further divided into three subgroups according to their previous experience with CNI: CNI-free, CNI withdrawal, and CNI conversion. Frequencies of blood Tregs were studied by flow cytometry after staining with monoclonal antibodies specific for different markers of Tregs.Results. Frequencies of CD4(+) T cells with regulatory phenotype and function were significantly decreased in peripheral blood of renal transplant patients receiving CNI compared with those receiving Rapa. This effect was independent of an early exposure to CNI because the CNI-free patients in the Rapa group showed similar frequencies of Tregs to the CNI withdrawal and CNI conversion groups.Conclusions. CNI, but not Rapa, induce a decrease of circulating Tregs in stable renal transplant recipients. Thus, Rapa might be further explored in strategies using preservation of Tregs for transplant tolerance. Furthermore, quantification of blood Tregs may be a suitable tool to identify renal transplant recipients who may be candidates for reduced immunosuppression.