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STUDY OF PATHOGENESIS IN AUTOIMMUNE INUJRY OF THE INNER EAR

内耳自身免疫性损伤发病机制的研究

基本信息

批准号：
10671621
负责人：
TOMIYAMA Shunichi
金额：
$ 2.05万
依托单位：
NIPPON MEDICAL SCHOOL
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
1998
资助国家：
日本
起止时间：
1998 至 2000
项目状态：
已结题

项目摘要

This study was designed to establish an experimental autoimmune labyrinthitis model in inbred mouse, which could exhibit high reproducibility and be adopted for precise immunological analysis. Following pretreatment with cyclophosphamide and primary sensitization with inner ear antigen (IEA) in FCA, many inflammatory cells transiently infiltrated into the whole area of the inner ear. This reaction occurred in all animals and peaked on day 12. This labyrinthitis was passively transferred by sensitized lymphocytes. Many CD4+ cells with IFN-γ+ and IL-2+ infiltrated mainly the endolymphatic sac as early as day 4, gradually into the whole area of the inner ear and persisted until day 35. On the other hand, very few CD8+ cells infiltrated on day 10 and rapidly disappeared. These results suggested that primary sensitization induce cellular autoimmune reaction in the inner ear mediated by helper T1 (Th1 ) lymphocytes. Repeated sensitization with IEA produced autoantibody to the inner ear. Western blot assay demonstrated three different serum antibodies, which reacted to 45, 66, 200 KD of the bovine inner ear antigen. IgG deposited mainly in the vessels of the stria vascularis and bone labyrinthine. Repeated sensitization with IEA stimulates humor mediated autoimmune reaction and autoantibody may alter morbid state of chronic stage of autoirmmune labyrinthitis. Immune reaction in the endolymphatic sac generates immune injury by nitric oxide, apoptotic degeneration, as well as sympathetic labyrinthitis.

本研究旨在建立自交系小鼠自身免疫性迷路炎的实验模型，该模型具有较高的重复性，可用于精确的免疫学分析。在FCA中，经过环磷酰胺预处理和内耳抗原（IEA）的初级致敏后，许多炎症细胞短暂地浸润到整个内耳区域。所有动物均出现这种反应，并在第12天达到高峰。这种迷路炎是由致敏淋巴细胞被动转移的。CD4+细胞以IFN-γ+和IL-2+为主，最早在第4天浸润内淋巴囊，逐渐进入整个内耳区域，并持续到第35天。另一方面，CD8+细胞在第10天很少浸润并迅速消失。这些结果表明，原致敏诱导由辅助性T1 （Th1）淋巴细胞介导的内耳细胞自身免疫反应。用IEA反复致敏产生内耳自身抗体。Western blot检测发现三种不同的血清抗体，分别对45、66、200 KD的牛内耳抗原产生反应。IgG主要沉积在血管纹和骨迷路的血管中。IEA反复致敏刺激幽默介导的自身免疫反应和自身抗体可改变自身免疫性迷路炎慢性期的发病状态。内淋巴囊免疫反应产生一氧化氮免疫损伤，细胞凋亡变性，交感迷路炎。