MyD88及Trif对心脏移植小鼠体内供者特异性抗体及记忆性T淋巴细胞的影响  

Effects of MyD88 and Trif on production of donor-specific antibodies and memory T cells in mouse cardiac transplant model

作　　者：王升[1] 王焦静[2] 明长生[1] 张政[2] 

机构地区：[1]华中科技大学同济医学院附属同济医院器官移植研究所,武汉430030 [2]美国西北大学Feinberg医学院器官移植实验室

出　　处：《中华器官移植杂志》2012年第9期556-558,共3页Chinese Journal of Organ Transplantation

摘　　要：目的探讨髓样分化因子88（MyD88）及Trif对皮肤移植预致敏的心脏移植小鼠体内供者特异性抗体（DSA）及记忆性T淋巴细胞的影响。方法实验分为空白组（C57BI。／6野生型小鼠，不行移植手术）、对照组（C3H小鼠为供者，C57BL／6小鼠为受者）和实验组（C3H小鼠为供者，MyD88及Trif基因敲除的C57BL／6小鼠为受者）。将C3H小鼠皮片移植给受鼠，进行预致敏，2周后检测受鼠血清中DSA的水平，并且将C3H小鼠心脏移植给相应受鼠，观察移植心脏存活时间。在观察终点时，再次检测受鼠血清中DSA水平，同时检测受鼠脾脏中记忆性T淋巴细胞的比例。结果皮肤移植2周后，实验组受鼠DSAIgG2水平低于对照组，差异有统计学意义（P〈0．05），DSAIgGl和IgG3的水平亦低于对照组，但差异无统计学意义（P〉0．05）。心脏移植3d后，与对照组相比较，实验组受鼠DSAIgG2水平明显降低（P〈0．01），受鼠脾脏中CD4＋和CD8＋记忆性T淋巴细胞的比例低于对照组（P〈0．01，P〈0．05）。两组受鼠心脏移植后平均存活时间的差异无统计学意义（P〉0．05）。结论敲除小鼠MyD88及Trif基因虽然不能延长预致敏小鼠移植心脏的存活时间，但是能显著降低受鼠血清中DSA的水平及脾脏中记忆性T淋巴细胞的比例。Objective To determine the roles of MyD88 and Trif, critical adaptor proteins for TLR signaling, in production of donor-specific antibodies （DSA） and memory T cells in a presensitized mouse cardiac transplant model. Methods Skin grafts from Balb/c mice were transplanted into either wild type If, mice or B6 Myd88 and Trif double knockout mice （Myd88/Trif DKO）. The recipients were subsequently transplanted heterotopically with cardiac grafts from the same donors two weeks after skin transplantation. Plasma DSA levels and spleen phenotypical analysis were performed prior to heart transplant or at time of cardiac rejection by using flow cytometry. Results Recipients presensitized with skin grafts developed accelerated cardiac allograft rejection in the absence of Myd88 and Trif. However, plasma DSA, especially IgG2, was significantly decreased （P^0. 05） in Myd88/ Trif DKO mice, compared to that in Wild Type mice at 2nd week after skin transplantation. The production of DSAs including all IgG subtypes was further reduced 3 days following heart transplantation in the Myd88/Trif DKO. In addition, MyD88/Trif DKO mice had impaired ability to generate memory T cells, as percentages of both CD44hi CD4＋ and CD44hl CD8＋ were significantly lower in the DKO than in Wild Type mice （P〈0. 01 ,P〈0. 05）. Conclusion Simultaneous ablation of MyD88 and Trif in recipients significantly decreases the production of serum DSAs and spleen memory T cells following aUogeneic skin and heart transplantation, supporting a crucial role of TLR signaling in adaptive immune responses in organ transplantation.

关 键 词：髓样分化因子88 TRIF 心脏移植 供体特异性抗体 记忆性T淋巴细胞 小鼠 

分 类 号：R654.2[医药卫生—外科学]