胰腺小岛的耐受性丧失是由贝塔细胞表达干扰素-马的诱导
N Sarvetnick1, J Shizuru, D Liggitt
1Department of Developmental Biology, Genentech, Inc., South San Francisco, California 94080.
Nature
|August 30, 1990
概括
在胰腺中,干扰素- (IFN-) 表达会通过促进淋巴细胞介导的胰腺小岛的破坏,导致自身免疫性糖尿病. 这项研究表明,IFN-gamma诱导了自我耐受性的丧失,导致免疫系统对正常小岛的攻击.
科学领域:
- 免疫学 免疫学 免疫学
- 内分泌学 在内分泌学.
- 分子生物学分子生物学
背景情况:
- 干扰素- (IFN-) 是免疫对感染反应中的关键细胞因子.
- 以前的研究表明,在胰岛素促进剂 (ins-IFN-gamma) 下表达IFN-的转基因小鼠患上糖尿病.
- 这种糖尿病的特点是由于炎症细胞透而导致胰腺小岛逐渐破坏.
研究的目的:
- 阐明IFN-gamma诱导的自身免疫糖尿病背后的特定免疫机制.
- 为了确定淋巴细胞是否介导ins-IFN-gamma小鼠的胰腺小岛的破坏.
- 研究IFN-在诱导胰腺小岛细胞自我耐受性丧失中的作用.
主要方法:
- 对ins-IFN-gamma小鼠的分析,以确定岛屿破坏的细胞媒介.
- 将基因相容小岛移植到ins-IFN-gamma小鼠中,以评估体内小岛的生存率.
- 在体外细胞毒性测试中,使用ins-IFN-玛小鼠的淋巴细胞与正常小岛.
主要成果:
- 在ins-IFN-gamma小鼠中,岛屿细胞损失是由淋巴细胞介导的.
- 在转基因接受者体内植入的基因相容小岛被破坏.
- 来自ins-IFN-gamma小鼠的淋巴细胞在体外表现出对正常小岛的直接细胞毒性.
结论:
- 胰腺对IFN-的表达可以破坏对小岛细胞的自我耐受性.
- IFN-的作用是诱导神经刺激活性,对于淋巴细胞激活至关重要.
- 这些发现凸显了IFN-gamma在启动对胰腺小岛的自身免疫反应中的作用.
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