他克莫司处理的供者树突状细胞延长大鼠移植心脏的存活时间

目的 研究经他克莫司(Tac)处理的供者未成熟树突状细胞(imEX3)在延长大鼠移植心脏存活时间中的作用和机制.方法 以Wistar大鼠为供者,SD大鼠为受者,行颈部异位心脏移植.心脏移植前将受者随机分为3组,每组15只,进行不同的预处理.第1组:为对照组,术前7 d经受者的尾静脉注射生理盐水1.0ml;第2组:为未经Tac处理组,术前7 d经受者的尾静脉注射未经Tac处理的imDC 2×106(1.0 m1);第3组:为Tac处理组,术前7 d经受者的尾静脉注射经Tac处理的imDC 2×106(1.0 m1).术后观察:移植心脏的存活时间、受者与供者及无关供者(Lewis大鼠)的单向混合淋巴细胞反应(MLR)、心肌组织病理学表现及血清中白细胞介素(IL)-2、IL-4、IL-10和γ干扰素(IFN-γ)的水平变化.结果 第1、2、3组移植心脏的存活时间分别为(8.57±1.34)d、(20.92±2.68)d和(33.30±3.92)d.各组之间比较,差异均有统计学意义(P＜0.01);第2、3组受者对供者的MLR刺激指数较第1组明显降低,而对无关供者的MLR刺激指数则与第1组相近;各组受者血清IL-2、IFN-γ、IL-4、IL-10浓度问差异有统计学意义(P＜0.01),第3组IL-2和IFN-γ(代表TH1细胞)水平明显降低,而IL-4和IL-10(代表TH2细胞)水平明显增高.结论 imDC能够延长大鼠心脏移植后的存活时间,经Tac处理的imDC能够进一步加强这种作用;且imDC所诱导的免疫低反应性是供者特异性的.其机制可能主要与调节T淋巴细胞免疫应答类型(TH1至TH2的免疫偏移)和诱导T淋巴细胞免疫应答降低有关.

The effect of donor dendritic cells treated with tacrolimus on prolonging rat cardiac allograft survival

Objective To study the effect of donor immature dendritic cells(imDCs)treated with Tacrolimus(TAC)on prolonging rat allograft survival and the action mechanism.Methods Cervical heart transplantations were performed in which Wister rats were used as donors,and SD rats as allograft recipients.Normal sodium(control group),imDCs(positive control group),and imDCs treated with TAG(TAC-treated group)were injected via vena caudalis 7 days before the operations respectively.Heart allograft survival was monitored and one-way MLR,heart pathology and the levels of IL-2,IL-4,IL-10,IFN-r in the serum were detected Results H test showed that there was high significant difference in heart allograft survival among the three groups(P＜0.01).Stimulation index in positive control and TAC-treated groups 2 and 3 in MLR was obviously lower than in control group,while stimulation index to independent donors in positive control and TAC-treated group were close to control group.Analysis of variance showed that there was high significant difference in serum concentrations of IL-2,IFN-r,IL-4,IL-10 among the three groups(P＜0.01).The concentrations of IL-2 and IFN-r being expressed on Thl were lower,and those of IL-4 and IL-10 being expressed on Th2 were obviously higher in positive control and TAC-treated groups.Conclusion ImDCs can prolong rat heterotopic cardiac allograft survival successfully;ImDCs treated with TAC can enhance the effect which is donor specific.ImDCs may induce the immune tolerance by means of modifying the immune response type of T cells(immune deflection from Th1 to Th2),and inducing T cells disenabling.