马奔 李霄 张卓超 纪洪辰 王璟 汪建林 杨西胜 王德盛 陶开山 窦科峰.供体来源ImDex 联合抗原特异性Treg保护大鼠肝脏移植物的研究[J].现代生物医学进展英文版,2015,15(3):453-457. |
供体来源ImDex 联合抗原特异性Treg保护大鼠肝脏移植物的研究 |
Exosomes fromDonor Derived Immature Dendritic Cells and Donor AntigenSpecial Regulatory T Cells Can Prolong Survival Time of Rat LiverAllograft |
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DOI: |
中文关键词: 调节性T细胞 外来体 树突状细胞 肝脏移植 |
英文关键词: Regulatory T cells Exosomes Dendritic cells Liver transplantation |
基金项目:国家自然科学基金青年项目(81300361);国家高技术研究发展计划"863" 计划项目( 2012AA021005);
陕西科学技术研究与发展计划(2013K12-18-02);西京医院助推计划(XJZT12M09;XJZT13Z01) |
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中文摘要: |
目的:探讨供体来源低剂量未成熟树突状细胞外来体(immature dendritic cells exosome, imDex)联合供体抗原特异型调节性
T 细胞(regulatory t cells, Tregs)对于肝脏移植物的保护作用。方法:以BN->Lewis 大鼠为供受体,建立大鼠原位肝移植模型。利用
超高速梯度离心法获得imDex,采用流式细胞术鉴定该imDex 的表型。不同剂量imDex 用于本移植模型,生存分析探究其对肝脏
移植物的保护作用及该作用与剂量的相关关系。利用磁珠分选技术获得Treg,混合淋巴细胞培养获得供体抗原特异性Treg,将不
同性质的Treg 用于移植受体,验证抗原特异性Treg保护肝脏移植物。进一步探究两者联合使用的效果,应用免疫荧光、流式细胞
术研究Treg 在移植受体中的分布。结果:超高速梯度离心法分选出的imDex 具有imDC 表型,其保护肝脏移植物的最佳作用剂
量为20 ug,Treg 发挥保护移植物作用具有抗原特异性。两者联合应用组生存时间长于对照组(P<0.05)。病理显示,输注的Treg
分布于受体移植物。结论:ImDex 联合抗原特异性Treg可以有效保护大鼠肝脏移植物。 |
英文摘要: |
Objective:To investigate the effect of donor derived imDex and donor antigen special Treg on the rat liver
transplantation.Methods:The orthotopic liver transplantation model in rats was established by using the BN/Lewis rats as donors and
recipients. Ultra high speed gradient centrifugation was utilized to obtain the imDex, and flow cytometry was used to identify the
phenotype of imDex. Different doses of imDex were used for the recipients, to explore the correlation between the doses of imDex and
the protective effect on the liver allograft through survival analysis. Treg was obtained with magnetic bead separation technology, then
using mixed lymphocyte culture, the donor antigen specially reactive Treg was obtained. Treg of different natures was used in transplant
recipients, to verify the protective effects of antigen specific Treg on liver grafts. Then combined use of both in recipients was carried out.
With the technologies of immunofluorescence and flow cytometry, the distribution of Treg in transplant recipients was determined.Results:Ultra high speed gradient centrifugation could isolate imDex and maintain the phenotype of imDC. The best effective dose of
imDex was 20 ug in rat liver transplantation. Treg had a protective role in the graft with antigen specificity. The survival time in the
combined application group was longer than that of the control group (P<0.05). Pathology of rat liver grafts showed the infused Treg was
distributed into the liver graft.Conclusion:ImDex combined with antigen specific Treg can effectively protect the rat liver graft, and both
have synergistic effect. |
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