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首页> 外文期刊>Journal of Surgical Research: Clinical and Laboratory Investigation >Transforming growth factor β1 and Fas ligand synergistically enhance immune tolerance in dendritic cells in liver transplantation
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Transforming growth factor β1 and Fas ligand synergistically enhance immune tolerance in dendritic cells in liver transplantation

机译：转化生长因子β1和Fas配体协同增强肝移植中树突细胞的免疫耐受性

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Abstract Background Long-term survival of patients following liver transplantation can be achieved by application of genetically modified, immune tolerogenic immature dendritic cells (imDCs) to overcome allograft-induced acute cellular rejection, a major cause of death. In this study, using a rat model of liver transplantation, we determined whether cotransfection of transforming growth factor β1 (TGF-β1) and Fas ligand (FasL) in imDCs synergistically enhances immune tolerance. Materials and methods We first determined the immune tolerogenic effects of TGF-β1 and FasL independently or together in imDCs by measuring the levels of CD86 and CD80 and by assessing T-cell proliferation using mixed lymphocyte reaction tests. Next, a rat model of liver transplantation, in which dark agouti and Lewis rats treated with DCs exogenously expressing TGF-β1 and/or FasL served as donors and recipients, respectively, was used to examine TGF-β1/FasL-induced immune tolerance. Specifically, we assessed the Banff rejection activity index (RAI), liver functions (alanine transaminase and total bilirubin levels), serum levels of interleukin (IL)-1, IL-10, and IL-12, apoptosis by TUNEL, and posttransplant survival. Results TGF-β1/FasL cotransfection of imDCs resulted in greater reduction of CD85 and CD80 expression and T-cell proliferation than a monotransfection. Cotransfected imDCs also showed reduced RAI scores, decreased plasma alanine transaminase and total bilirubin, altered cytokine levels, increased apoptosis, and prolonged survival than monotransfected imDCs in liver-allografted rats. Conclusions By enhancing immune tolerance, reducing liver damage, and achieving long-term postsurgery survival, TGF-β1/FasL cotransfection of imDCs may prove more beneficial for patients undergoing liver transplantation.
机译：摘要肝移植后患者的长期存活可以通过应用遗传修饰，免疫耐受性未成生树突细胞（IMDC）来克服同种异体移植诱导的急性细胞排斥，是死亡的主要原因。在该研究中，使用肝移植的大鼠模型，我们确定在IMDC中转化生长因子β1（TGF-β1）和Fas配体（FasL）的COT次反应协同增强免疫耐受性。通过测量CD86和CD80的水平，通过测量使用混合淋巴细胞反应试验，首先通过测量CD86和CD80的水平，在IMDC中独立地或在IMDC中的免疫耐受性效应。接下来，使用肝移植的大鼠模型，其中分别用DCs外源表达TGF-β1和/或FASL处理的DCS和Lewis大鼠作为供体和接受者的DC处理，用于检查TGF-β1/ FasL诱导的免疫耐受性。具体而言，我们评估了班夫排斥活动指数（RAI），肝功能（丙氨酸转氨酶和总胆红素水平），白细胞介素（IL）-1，IL-10和IL-12，受TUNEL的细胞凋亡和后移植物生存率。结果IMDC的TGF-β1/ FasL COT转酵母导致CD85和CD80表达和T细胞增殖的减少更低。 Cotransfacted IMDC还显示RAI评分减少，降低血浆丙氨酸转氨酶和总胆红素，细胞因子水平改变，细胞凋亡增加，延长的存活率比肝 - 同种异体移植大鼠的单次IMDC。结论通过增强免疫耐受性，降低肝脏损伤，以及实现长期前列生存率，IMDC的TGF-β1/ FasL COT转酵母可能对接受肝移植的患者进行更有益。

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