NBD多肽预处理的树突状细胞延长移植心存活时间的实验研究  

Pretreatment of donor dendritic cells with NBD-peptide prolongs mouse cardiac allograft survival

作　　者：苏刚[1] 赵文增 陈家军[2] 徐静[1] 乔晨晖[1] 刘超[1] 孙宗全[2] 

机构地区：[1]郑州大学第一附属医院心血管外科,河南郑州450052 [2]华中科技大学同济医学院附属协和医院心血管外科,湖北武汉430022

出　　处：《南方医科大学学报》2008年第9期1562-1567,共6页Journal of Southern Medical University

基　　金：国家自然科学基金(30471715);郑州大学博士启动基金

摘　　要：目的探讨NBD多肽预处理的供体源性树突状细胞(DC)在诱导心脏移植免疫耐受中的作用及可能机制。方法体外培养供体源性BALB/c小鼠骨髓树突状细胞并以NBD多肽预处理(NBD多肽-DC,在小鼠心脏移植前7 d,将NBD多肽-DC输至受者C57BL/6小鼠体内。应用Cu-T建立小鼠颈部异位心脏移植模型,观察心脏移植物存活时间,病理分析检测排斥反应程度,混合淋巴细胞反应(MLR)测定受者脾脏T细胞对供者同种抗原的反应性,并用ELISA方法测定受者血清Th1型细胞因子(IFN-γ和IL-12)和Th2型细胞因子(IL-4和IL-10)水平的变化。结果NBD多肽-DC可使移植心脏存活天数延长至(21.83±3.54)d,较PBS对照组的(6.66±1.21)d明显延长(P<0.01),降低排斥反应病理分级(Stanford 1～2级),能诱导受者脾脏T细胞的抗原特异性低反应性,使受者小鼠血清INF-γ和IL-12水平显著降低(P<0.01),而IL-4和IL-10水平明显升高(P<0.01)。结论NBD多肽预处理的供体源性DC能够诱导针对移植供者产生的特异性免疫耐受现象,其机制可能与诱导受者T细胞的抗原特异性低反应性及Th1/Th2免疫偏移有关。Objective To observe the effects ofNBD-peptide pretreatment of the donor dendritic cells in immune tolerance induction in mouse allograft recipients and investigate the mechanisms. Methods BALB/c mouse DCs pretreated with NBD-peptide （NBD-Peptide-DC） were injected into the recipient C57BL/6 mice 7 days before transplantation. Cervical heterotopic heart transplantation model was established using the cuff technique and the cardiac allograft survival time was observed. Pathological analysis were performed to examine the graft injection and the responsiveness of the recipient spleen T cell to the donor alloantigen was determined by mixed lymphocyte reaction （MLR）. The serum levels of cytokines were determined using ELISA. Results The cardiac allograft survival time in the NBD-Peptide-DC-treated group （21.83±3.54 days） was significantly longer than that in the Day9-DC group （13.33±2.58 days） and PBS-treated group （6.66± 1.21 days） （P〈0.01）, with also significantly lower pathological grade for graft rejection （P〈0.01）. The donor-derived NBD-Peptide-DCs induced alloantigen-specific T-cell hyporesponsiveness. In the NBD-Peptide-DC-treated group, the serum levels of IL-12 and IFN-γ decreased significantly （P〈0.01）, but the levels of IL-4 and IL-10 increased significantly （P〈0.01）. Conclusion Injection of donor-derived NBD-Peptide-DCs can leads to donor-specific tolerance in the transplant recipients, and the induction of recipient T-cell hyporesponsiveness and polarization of Th2 response may play important roles in immune tolerance to cardiac allografts.

关 键 词：NBD多肽 树突状细胞 免疫耐受 心脏移植 排斥反应 

分 类 号：R654.2[医药卫生—外科学]