Models for studying mechanism of autoimmune disease

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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.