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

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

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。

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.