The role of liver in donor-specific immunotolerance

肝脏在供体特异性免疫耐受中的作用

• 批准号: 14571120
• 负责人: DOI Hideyuki
• 金额: $ 2.05万
• 依托单位: TOHOKU University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2002
• 资助国家: 日本
• 起止时间: 2002 至 2003
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-14571120/
• 关键词: thymus; immunotolerance; liver; 胸腺上皮細胞; 胸腺ナース細胞; キメリズム; クッパー細胞

(1)In rat model, ACI thymus cluster was inoculated into subcutaneous, intravenous, and into portal vein of Lewis rats. 7days after inoculation, Lewis rats received ACI cardiac graft. No treated group rejected in 3 to 6 days after transplantation, subcutaneous inoculation shortened survival time, but i.v. inoculation prolonged survival for 1-3days, p.v. inoculation prolonged survival more than 7days. However, there is no significant difference between lymphocyte inoculation and cluster inoculation into the liver.(2)In mouse model, Balb/c thymus cluster was inoculated into subcutaneous, intravenous, and into portal vein of B6 mice. 7days after inoculation mixed lymphocyte culture was done between B6 mouse and inoculated Balb/c mouse. subcutaneous inoculation sensitized MLR reaction, but i.v. inoculation and p.v. inoculation suppressed MLR reaction. However, there is no significant difference between lymphocyte inoculation and cluster inoculation into the liver.(3)We could not find micro chimerism in any lymph organs of Lewis rat which was inoculated ACI thmus cluster into the liver.(4)Diabetes was induced by veneous injection of streptozotcin. We examined a number of islet necessary for normalizing he blood sugar. The results showed that the blood sugar normalized by 20IQ(islet equivalent) or more.(5)The islets and the cluster were injected into portal vein simultaneously, and the acquisition of immunotolerance was examined. The animals were hardly found to die in the clusters or ilets single transplantation. However, the simultaneous injection was found to cause portal embolism and sudden death of rats. Although we tried various experimental protocols, the embolism was not improved by any experimental procedures.

(1)在大鼠模型中，将ACI胸腺团接种于Lewis大鼠的皮下、静脉和门静脉。接种后7d，Lewis大鼠接受ACI心脏移植。治疗组在移植后3~6天内无排斥反应，皮下接种可缩短存活时间，但静脉注射。接种可延长1-3天的存活时间，P.V.接种后存活时间延长7天以上。在小鼠模型中，将Balb/c胸腺簇团接种于B6小鼠皮下、静脉和门静脉。接种7d后，对B6小鼠和Balb/c小鼠进行混合淋巴细胞培养。皮下接种可致敏MLR反应，但静脉注射致敏。接种和P.V.接种抑制了MLR反应。而肝内接种淋巴细胞和簇状接种的差异无统计学意义。(3)经肝内接种ACI-thus后，Lewis大鼠的任何淋巴器官均未发现微嵌合体。(4)静脉注射链脲佐菌素诱发糖尿病。我们检查了一些使血糖正常化所必需的胰岛。结果表明，血糖达到或超过20IQ(胰岛当量)。(5)将胰岛和胰岛簇同时注入门静脉，检测免疫耐受的获得。这些动物几乎没有在集群或Ilet单次移植中死亡。然而，同时注射可引起大鼠门静脉血栓和猝死。虽然我们尝试了各种实验方案，但任何实验程序都没有改善栓塞率。