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)建立抗原特异性耐受及其破裂的动物模型。今年，我们主要做了以下几个方面的工作：(1)给予OVA特异性TCR-TG后，未经OVA注射的小鼠脾细胞可检测到Th1型细胞因子的抑制产生。这种抑制作用可通过加入IL-2而恢复。小鼠血清免疫球蛋白E水平也明显降低。在以前使用非TCR-TG的系统中，诱导耐受需要抗原启动，因此，在何时何地获得耐受一直不清楚。这一问题在目前的制度中已得到澄清。(2)将OVA转基因细胞移植到TCR-TG中，成功建立了另一种耐受系统。此外，还产生了OVA转基因小鼠，其表达正在检测中。这些小鼠是研究自身反应性T细胞耐受性及其破坏机制的更合适的模型。

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.