Liver Transplantation Center, Third Affiliated Hospital, Transplantation Research Institute, Sun Yat-Sen University, Organ Transplantation Research Center of Guangdong Province, Guangzhou 510630, China.
Hepatobiliary Pancreat Dis Int. 2012 Apr;11(2):203-8. doi: 10.1016/s1499-3872(12)60149-0.
Dendritic cells (DCs) can initiate the expansion of regulatory T cells (Tregs), which play an indispensable role in inducing transplantation tolerance. Some studies have investigated the effect of the immunosuppressant rapamycin (Rapa) on Tregs in vitro. However, the in vivo effect of Rapa combined with immature DCs (iDCs) on Tregs is unknown. This study was undertaken to determine whether allogenic iDCs combined with a short course of Rapa have the ability to selectively expand the CD4+CD25+Foxp3+ Tregs in a rat model.
Brown Norway rats were injected intravenously with 2X10(6) Lewis iDCs followed by 1 mg/kg per day Rapa intraperitoneally for 7 consecutive days. On day 8, the levels of CD4+CD25+Foxp3+ Treg cells in peripheral blood and spleen cells were analyzed by flow cytometry. IL-2, IL-4, TGF-beta1, and IFN-gamma levels in serum were assessed by ELISA. The experimental animals were divided into four groups: control, Rapa-treated, iDC-treated, and combination-treated.
CD4+CD25+Foxp3+ Tregs comprised 7%-8% of CD4+ T cells in control rats. Rapa combined with iDCs enhanced this percentage in the peripheral blood and spleen. However, the levels of Tregs did not significantly change after treatment with Rapa or iDCs alone. The levels of CD4+CD25-Foxp3+ T cells and CD4+CD25+Foxp3- T cells in CD4+ T cells did not significantly change in the combined group. The TGF-beta1 level in serum from the combined group increased significantly compared with the other groups.
A significantly higher percentage of CD4+ CD25+ Foxp3+ Tregs was found in rats treated with allogenic iDCs and a short course of Rapa, along with an increase in the TGF-beta1 level in serum. This improved protocol may be a promising therapeutic strategy to increase Tregs, which are beneficial to the induction of peritransplant tolerance.
树突状细胞（DCs）可启动调节性 T 细胞（Tregs）的扩增，Tregs 在诱导移植耐受中起着不可或缺的作用。一些研究已经在体外研究了免疫抑制剂雷帕霉素（Rapa）对 Tregs 的影响。然而，Rapa 联合未成熟 DC（iDCs）对 Tregs 的体内作用尚不清楚。本研究旨在确定同种异体 iDCs 联合短期 Rapa 是否具有在大鼠模型中选择性扩增 CD4+CD25+Foxp3+Tregs 的能力。
Brown Norway 大鼠静脉注射 2X10(6)Lewis iDCs，随后腹腔内注射 1mg/kg Rapa，连续 7 天。第 8 天，通过流式细胞术分析外周血和脾细胞中 CD4+CD25+Foxp3+Treg 细胞的水平。通过 ELISA 评估血清中 IL-2、IL-4、TGF-β1 和 IFN-γ的水平。实验动物分为四组：对照组、Rapa 处理组、iDC 处理组和联合处理组。
对照组大鼠 CD4+T 细胞中 CD4+CD25+Foxp3+Treg 占 7%-8%。Rapa 联合 iDCs 可增强外周血和脾中这一比例。然而，Rapa 或 iDCs 单独治疗后 Treg 水平没有显著变化。在联合组中，CD4+CD25-Foxp3+T 细胞和 CD4+CD25+Foxp3-T 细胞在 CD4+T 细胞中的水平没有明显变化。与其他组相比，联合组血清中 TGF-β1 水平显著增加。
同种异体 iDCs 和短期 Rapa 治疗大鼠后，CD4+CD25+Foxp3+Treg 的比例显著升高，同时血清中 TGF-β1 水平升高。这种改良方案可能是一种有前途的治疗策略，可增加 Tregs，有利于诱导移植耐受。
