不同免疫治疗方案诱导大鼠原位肝移植免疫耐受的实验研究

目的 观察抗CD-40L单抗加小剂量CsA联合免疫治疗对肝移植大鼠受体免疫耐受诱导的作用.方法 在建立稳定大鼠肝移植模型的基础上,将肝移植模型分为5组.A组为SD→SD对照组;B组为SD→Wistar对照组,A,B组术后不用任何治疗措施;C组为SD→Wistar,术后用CsA1～5 d;D组为SD→Wistar,术后用CsA 1～5 d加抗CD-40L(CD-154)单抗0～2d;E组为D组+术前供体特异性输血(DSBT).观察受体存活时间、移植肝病理改变以及术后外周血中细胞因子的变化.结果 A,D,E组受体大鼠存活时点(均>60 d)均明显长于B组和C组.D,E组移植肝急性排斥反应明显减轻.B组IL-2和IFN-γ的血清水平显著高于其余各组(P＜0.05).B,C,D,E 4组IL-4和IL-10较A组均有明显增加,尤其D,E组的IL-10表达较B组显著增高(P＜0.05). 结论 抗CD-40L单抗加小剂量CsA(伴或不伴DSBT)联合免疫治疗,可有效延长肝移植大鼠受体生存时间、减轻急性排斥反应并诱导Th2类细胞因子的高水平表达,有助于受体和移植肝的长期存活.

Study of different immunotherapy plans in the induction of immune tolerance in orthotopic liver transplantation in the rat

Abstract:Objective:To study the influence of combined anti-CD-40L and low dose CsA immunotherapy on the induction of immune tolerance in orthotopic liver transplantation rats.Methods :Recipients were divided into the following groups. Group A,SD→SD; Group B,SD→Wistar without any treatment; Group C,SD→Wistar with CsA therapy from d1 to d5; Group D,SD→Wistar with CsA from d1 to d5 and anti-CD40L mAb in d0 and d2, and Group E,SD→Wistar with CsA from d1 to d5 and anti-CD40L mAb in d0 and d2 plus autotransfusion before operation. The recipient survival time, histologic changes of allograft and the level of cytokines in peripheral blood were observed.Results:The survival period of recipients in Groups A, D and E was significantly longer than that in Groups B and C. The acute rejection response in Groups D and E decreased prominently. The serum level of IL-2 and IFN-γ in Group B were significantly higher than those in other groups, while the serum level of IL-4 and IL-10 in Groups D and E was elevated much more than those in Group B(P＜0.05).Conclusions:The combined anti-CD-40L and low dose CsA immunotherapy with or with autotransfusion can prolong graft survival time, suppress acute rejection and induce high expression of Th2 cytokines, and is beneficial to long-term survival of recipients and liver graft.