IFN-γ对小鼠心脏移植免疫耐受的影响

The impact of IFN-γ on cardiac transplant tolerance in mice

目的探讨γ干扰素(IFN-γ)对阻断共刺激信号CD40-CD40配体所诱导的小鼠心脏移植免疫耐受的作用。方法移植心脏和脾脏取自行心脏移植后的同种同系受体和同种异系受体(包括接受和未接受抗CD40配体抗体治疗),使用实时定量RT-PCR方法测定IFN-γ的表达。比较野生型小鼠和IFN-γ基因去除小鼠受体移植物的存活时间。同时比较接受MR-1治疗的野生型小鼠受体和IFN-γ基因去除小鼠受体的CD4+T细胞混合淋巴细胞反应和CD8+T细胞的细胞毒性。结果发生排斥反应的移植物较免疫耐受移植物表达更高的IFN-γ。IFN-γ基因去除小鼠受体如未接受免疫抑制治疗,移植物存活时间无明显延长,较之野生型小鼠受体反而有所缩短。使用MR-1在野生型小鼠受体中诱导出移植物的长期存活,但在IFN-γ基因去除小鼠受体中却无类似效果。IFN-γ缺失使T细胞的增殖活性及细胞毒性增强。结论在阻断共刺激信号CD40-CD40配体所诱导的移植免疫耐受中,IFN-γ能够促进免疫耐受状态的形成。

Objective To investigate the impact of IFN-γ on cardiac transplant tolerance induced by blockade of CD40-CD40 ligand costimulation pathway in mice. Methods IFN-γ expression in cardiac grafts and spleens from syngeneic and allogeneic recipients with or without treatment of anti-CD40 ligand monoclonal antibody（MR-1） was examined by realtime RT-PCR.The survival time of cardiac grafts in Wild type and IFN-γ-deficient recipients was investigated.Mixed lymphocyte reaction（MLR） of CD4＋T cells and cytotoxic T lymphocyte assay of CD8＋T cells from Wild type recipients and IFN-γ-deficient recipients administrated with MR-1 were also studied. Results Rejected cardiac allogafts showed significantly higher expression of IFN-γ than tolerant allogafts.Cardiac allograft survival was not prolonged in nonimmunosuppressed IFN-γ-deficient mice.In fact,graft survival time in IFN-γ-deficient mice was somewhat shorter than that observed in Wild type recipients.Administration of MR-1 induced long-term cardiac allograft survival in Wild type recipients,but failed to do so in the IFN-γ-deficient group.Our results also provided evidence that in vivo absence of IFN-γ in recipients facilitated the proliferation and CTL generation of T cells. Conclusions IFN-γ faciliates the formation of transplant tolerance induced by blockade of CD40-CD40 ligand costimulation pathway.