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IL-10对小鼠移植免疫耐受的影响

Impact of IL-10 on the mouse transplant immune tolerance
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摘要 目的 :探讨白细胞介素10(IL-10)对阻断共刺激信号CD40-CD40配体(CD40-CD40L)所诱导的小鼠移植免疫耐受的影响。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(MR-1)治疗],使用实时定量RT-PCR方法测定IL-10的表达。比较野生型小鼠和IL-10基因去除小鼠受体移植物的存活时间。同时通过使用IL-10受体单克隆抗体(anti-IL-10R m Ab)阻断IL-10信号以研究IL-10对CD4^+T细胞混合淋巴细胞反应、CD8^+T细胞的细胞毒性及树突状细胞(DCs)的免疫抑制活性的影响。结果:移植免疫耐受的移植物较发生排斥反应的移植物表达更高的IL-10。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IL-10基因去除小鼠受体中却无类似效果。IL-10缺失使T细胞的增殖活性及细胞毒性增强,而DC的免疫抑制活性下降。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,IL-10能够促进免疫耐受状态的形成。 Objective: To investigated the impact of IL-10 on the mouse transplant immune tolerance induced by blockade of CD40-CD40 ligand costimulation pathway. Methods: IL-10 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 IL-10 deficient recipients was investigated. Mixed lymphocyte reaction (MLR) ofCD4+Tcells,cytotoxicTlymphocyteassayofCD8+Tcells and suppressive capability of dendritic cells(DCs) were also studied. Results: Tolerant cardiac allogafts showed significantly higher expression of IL-10 than rejected allogafts. Administration of MR-1 induced long-term cardiac allograft survival in Wild type recipients but failed to do so in the IL-lO deficient group. Our results also provided evidence that the absence of IL-IO facilitated the proliferation and CTL generation of T cells. Furthermore, in vivo absence of IL-10 decreased the suppressive capability of DCs. Conlusion: IL-lO is essential for the long-term allograft survival induced by blockade of CD40-CD40 ligand costimulation pathway.
出处 《中国现代普通外科进展》 CAS 2015年第11期851-855,共5页 Chinese Journal of Current Advances in General Surgery
基金 辽宁省自然科学基金项目(2014021048)
关键词 白细胞介素10 共刺激信号 小鼠心脏移植 免疫耐受 IL-10 Costimulation pathway Mouse heart transplantation Tolerance
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