Models for studying mechanism of autoimmune disease

本课题旨在利用T细胞受体转基因小鼠（TCR-Tg）建立抗原特异性免疫耐受及其破坏的动物模型。今年，我们主要尝试了容忍诱导系统，并取得了以下成果。(1)在OVA饲养的OVA特异性TCR-Tg，抑制生产的Th 1型细胞因子在脾细胞中检测到没有引发的OVA注射。这种抑制作用通过加入IL-2而恢复。小鼠血清IgE水平也降低。在以前使用非TCR-Tg的系统中，需要抗原引发以诱导耐受，因此，不清楚何时以及在何处获得耐受。这个问题在现行制度中得到澄清。(2)另一种耐受系统通过将OVA转染子移植到TCR-Tg中而成功。此外，还制备了OVA tg小鼠，并对其表达进行了检测。这些小鼠是研究自身反应性T细胞耐受及其破坏机制的理想模型。

In this project, we aimed to obtain the animal model with antigen specific tolerance and its break using T cell reseptor trangenic mice (TCR-Tg). This year, we have mainly tried to make the tolerance-induction system and resulted in the followings. (1) In OVA feeded OVA-specific TCR-Tg, suppressive production of Th1-type cytokines was detectable in spleen cells without priming of OVA injection. This suppresive effect was recovered by adding IL-2. The serum level of IgE level was also reduced in the mice. In previous system using non-TCR-Tg, antigen priming is required for inducing tolerance, and consequently, it has been unclear when and where tolerance is acqired. This issue was clarified in the present system. (2) Another tolerance system was succeeded by transplantation of OVA transfectants in the TCR-Tg. Furthermore, OVA tg mice were produced and its expression is under examination. These mice are more appropriate model for investigating tolerance and its breaking-mechanism of auto-reactive T cells.