Department of Clinical Immunological Laboratory, West China Hospital, Sichuan University, Chengdu 610041, PR China.
Int Immunopharmacol. 2011 Dec;11(12):2033-8. doi: 10.1016/j.intimp.2011.08.015. Epub 2011 Sep 10.
Calcineurin inhibitors (CNI) prevent graft rejection by blocking interleukin-2 (IL-2), which was required for development and function of Foxp3(+)CD4(+)CD25(+) regulatory T cells (Treg). Recently, IL-2 was reported to play a part in the inhibition of Th17 cells. The renal transplantation recipient who used CNI regularly might have Th17/Treg imbalance with increased Th17 cells and decreased Treg cells, which would cause renal dysfunction even rejection. To assess the effect of CNI on Th17 cells and Treg cells, we included 123 renal transplantation recipients (101 in a stable stage and 22 with renal dysfunction) and 27 healthy volunteers. Among all the recipients, 103 recipients used CNI and 20 recipients used sirolimus without CNI. The recipients who used CNI were further classified into four groups according to the blood levels of CNI: Of all these subjects, Th17 and Treg frequencies in the peripheral blood were analyzed by flow cytometry (FCM). Serums IL-17, IL-23, IL-6, IFN-r, and TGF-β were analyzed by ELISA. The results demonstrated that the transplantation recipient treated by CNI revealed an obvious increase in peripheral Th17 frequencies and a significant decrease in Treg frequencies when compared with the sirolimus group and healthy people (P<0.05). Even more, the transplantation recipient with renal dysfunction had the highest level of Th17 cells (P<0.05) while the lowest Treg cells compared with stable recipient and healthy control, with increased serums IL-6 and IL-17. Our results indicated that CNI was associated with Th17/Treg imbalance in peripheral blood, which supported the followed generation of renal dysfunction after transplantation.
钙调磷酸酶抑制剂（CNI）通过阻断白细胞介素-2（IL-2）来预防移植物排斥反应，而白细胞介素-2（IL-2）是 Foxp3(+)CD4(+)CD25(+)调节性 T 细胞（Treg）发育和功能所必需的。最近，有报道称白细胞介素-2（IL-2）在抑制 Th17 细胞中发挥作用。经常使用 CNI 的肾移植受者可能存在 Th17/Treg 失衡，表现为 Th17 细胞增加和 Treg 细胞减少，这会导致肾功能障碍甚至排斥反应。为了评估 CNI 对 Th17 细胞和 Treg 细胞的影响，我们纳入了 123 名肾移植受者（101 名处于稳定期，22 名肾功能障碍）和 27 名健康志愿者。在所有受者中，103 名受者使用 CNI，20 名受者使用西罗莫司而不使用 CNI。根据 CNI 的血药浓度，将使用 CNI 的受者进一步分为四组：通过流式细胞术（FCM）分析所有这些受试者外周血中的 Th17 和 Treg 频率。通过 ELISA 分析血清 IL-17、IL-23、IL-6、IFN-r 和 TGF-β。结果表明，与西罗莫司组和健康人相比，使用 CNI 的移植受者外周血 Th17 频率明显增加，Treg 频率明显降低（P<0.05）。更重要的是，与稳定受者和健康对照组相比，肾功能障碍的移植受者具有最高水平的 Th17 细胞（P<0.05），而 Treg 细胞最低，同时伴有血清 IL-6 和 IL-17 增加。我们的结果表明，CNI 与外周血中的 Th17/Treg 失衡有关，这支持了移植后肾功能障碍的发生。
