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New Development of Multiple Autoimmune Diseases in Neonatally Thymectomized Autoimmune Mice

新生胸腺切除自身免疫小鼠多种自身免疫性疾病的新进展

基本信息

批准号：
01570208
负责人：
TAGUCHI Osamu
金额：
$ 1.41万
依托单位：
Aichi Cancer Center
依托单位国家：
日本
项目类别：
Grant-in-Aid for General Scientific Research (C)
财政年份：
1989
资助国家：
日本
起止时间：
1989 至 1990
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-01570208/
关键词：
Mouse Thymectomy Autoimmune disease 胸線摘除

项目摘要

NZB/NZWF1 (BWF1) and MRL/Mp-1pr/1pr (MRL/1pr) mice spontaneously develop a disorder resembling human systemic lupus erythematosus (SLE). The non-obese diabetic (NOD) mouse, a model of human insulin dependent diabetes mellitus, develops autoimmune insulitis. We have been reported that spontaneous development of organ-localized autoimmune diseases, such as thyroiditis, gastritis, in day 3 thymectomized (Tx-3) standard mice such as BALB/c and A/J mice. Such autoimmune diseases does not develop in Tx-7 mice. The purpose of this investigation was to examine the role of the thymus in the various mice that spontaneously developing SLE and insulitis. Development of glomerulonephritis and polyarthritis was found in Tx-3 BWF1 and MRL/1pr mice. The incidence and severity of these lesions were almost same to those of non-Tx mice. Organ-licolized autoimmune diseases, such as gastritis and oophoritis, were found in these Tx-3 mice. Together indicating that effector T cells for induction of both systemic and organ-localized autoimmune diseases were peripheralized from the thymus at early neonatal age. Multiple development of organ-localized autoimmune diseases were found in Tx-3 NOD mice. Such autoimmune diseases were also found in Tx-7 and Tx-14 mice indicating the functional abnormality of the thymus. The incidence and severity of insulitis in Tx-3 NOD mice were lower than those of untreated mice. Post-Tx autoimmune lesions were prevented by splenic T cells with L3T4 phenotype obtained from syngeneic normal mice.

NZB/NZWF 1（BWF 1）和MRL/Mp-1 pr/1 pr（MRL/1 pr）小鼠自发地发展类似于人类系统性红斑狼疮（SLE）的疾病。非肥胖型糖尿病（NOD）小鼠是人类胰岛素依赖型糖尿病的模型，可发生自身免疫性胰岛炎。我们已经报道了在第3天胸腺切除（Tx-3）的标准小鼠如BALB/c和A/J小鼠中自发发生器官局部自身免疫性疾病，如甲状腺炎、胃炎。这种自身免疫性疾病不会在Tx-7小鼠中发展。本研究旨在探讨胸腺在自发性SLE和胰岛炎小鼠中的作用。在Tx-3 BWF 1和MRL/1 pr小鼠中发现肾小球肾炎和多关节炎的发展。这些病变的发生率和严重程度与非Tx小鼠几乎相同。在这些Tx-3小鼠中发现了诸如胃炎和卵巢炎的器官化自身免疫性疾病。这表明诱导全身性和器官局部自身免疫性疾病的效应T细胞在新生儿早期从胸腺外周化。在Tx-3 NOD小鼠中发现了多种器官定位的自身免疫性疾病的发展。在Tx-7和Tx-14小鼠中也发现了这种自身免疫性疾病，表明胸腺功能异常。Tx-3 NOD小鼠胰岛炎的发生率和严重程度低于未治疗小鼠。Tx后自身免疫性病变被从同基因正常小鼠获得的具有L3 T4表型的脾T细胞预防。