背景:诱导供者特异性免疫耐受被认为是最终克服器官移植后排斥反应的有效途径,近年来关于未成熟树突状细胞在诱导免疫耐受中的重要作用日益受到关注。目的:观察他克莫司处理的供者未成熟树突状细胞对大鼠同种异体心脏移植免疫耐受的影响,分析未成熟树突状细胞诱导免疫耐受的作用途径。设计:随机对照动物实验。材料:实验于2006-04/2006-12在青岛大学医学院附属医院动物实验中心完成。以45只Wistar大鼠为供体,45只SD大鼠为受体,行颈部心脏移植45例次。按随机数字表法分为3组,每组15例次,进行不同的预处理。方法:对照组、未经他克莫司处理组及他克莫司处理组移植前7d分别经尾静脉注射生理盐水、供者未成熟树突状细胞和他克莫司处理的未成熟树突状细胞。分别测定移植后SD大鼠与Wistar大鼠及第3品系Lewis大鼠的单向混合淋巴细胞反应。主要观察指标:各组受体大鼠移植心脏存活时间、心肌病理及血清白细胞介素2、白细胞介素4、白细胞介素10、γ-干扰素含量变化。结果:①未经他克莫司处理组大鼠的移植心脏存活时间较对照组明显延长(P<0.01),他克莫司处理组大鼠的移植心脏存活时间进一步延长(P<0.05)。②混合淋巴细胞培养结果显示为供者特异性。③各组大鼠血清白细胞介素2、γ-干扰素、白细胞介素4、白细胞介素10含量差异具有显著性意义(P<0.01)。代表Th1的白细胞介素2、γ-干扰素水平明显降低,代表Th2的白细胞介素4、白细胞介素10水平明显增高。结论:未成熟树突状细胞能够诱导同种异体大鼠心脏移植免疫耐受;他克莫司处理的未成熟树突状细胞能够加强这种免疫耐受,且这种耐受是供者特异性的。其可能主要通过调节T细胞免疫应答类型(Th1至Th2的免疫偏移)、诱导调节性T细胞和诱导T细胞失能等途径来参与免疫耐受的形成。 BACKGROUND: Induction of donor-specific immune tolerance is considered as an effective way to finally overcome the rejection after organ transplantation. In recent years, the important role of immature dendritic cells in inducing immune tolerance has drawn increasing attention. OBJECTIVE: To observe the effect of immature dendritic cells donated by tacrolimus on the immune tolerance of allogeneic heart transplantation in rats, and to analyze the role of immature dendritic cells in inducing immune tolerance. Design: Randomized controlled animal experiments. MATERIALS: Experiments were performed at Animal Experimental Center, Affiliated Hospital of Qingdao University Medical College from April 2006 to December 2006. Forty-five Wistar rats were used as donors, 45 SD rats as recipients and 45 cases of cervical heart transplantation. According to random number table divided into 3 groups, each group of 15 cases, for different pretreatment. Methods: In the control group, saline and donor immature dendritic cells and immature dendrites treated with tacrolimus were administered 7 days before transplantation without tacrolimus and tacrolimus Cells. The unidirectional mixed lymphocyte reaction was measured in the transplanted SD rats and Wistar rats and in the third rat Lewis rats. MAIN OUTCOME MEASURES: Cardiac survival time, myocardial pathology and changes of serum interleukin 2, interleukin 4, interleukin 10, interferon - γ in recipients of each group were observed. Results: ① The survival time of transplanted heart in rats without tacrolimus treatment was significantly longer than that in control group (P <0.01). The survival time of transplanted heart in tacrolimus-treated rats was further prolonged (P <0.05). ② mixed lymphocyte culture showed donor-specific results. ③ The levels of serum interleukin 2, interferon-γ, interleukin-4 and interleukin-10 in each group had significant difference (P <0.01). Interleukin 2, which represents Th1, was significantly reduced in the presence of interferon-gamma, representing an increase in Th2 interleukin-4 and interleukin-10 levels. CONCLUSION: Immature dendritic cells can induce allograft immune tolerance in allograft rats; immature dendritic cells treated with tacrolimus potentiate this immune tolerance and this tolerance is donor specific Sexual. It may participate in the formation of immune tolerance mainly through regulating the types of T cell immune response (Th1 to Th2 immune offset), inducing regulatory T cells and inducing T cell disability.