Molecurar immunological study of VKH disease

我们已报道酪氨酸酶家族蛋白可诱发类似于Vogt-Koyanagi Harada病(VKH)的自身免疫性疾病。VKH患者PBMC中的淋巴细胞在酪氨酸酶家族蛋白的作用下增殖。这些结果表明酪氨酸酶家族蛋白是VKH的特异性抗原。在本项目中，我们进一步证实了这些结果，并研究了VKH中涉及的免疫反应。为了阐明VKH中自身反应性T细胞的发育和分化，我们正在建立表达酪氨酸酶的转基因Lewis大鼠。Lewis大鼠缺乏酪氨酸酶，但对各种自身免疫性疾病敏感。在不同器官和不同时期表达酪氨酸酶的Lewis大鼠将有效地研究中枢和外周对自身抗体的耐受性。我们计划制作在Arrestin启动子下表达酪氨酸酶的转基因大鼠，该基因启动子用于视网膜特异性表达，β-肌动蛋白用于普遍表达，酪氨酸酶用于黑素细胞。我们现在正在制作携带转基因的大鼠的兄弟姐妹。

We have reported that tyrosinase family protein can induce autoimmune disease similar to Vogt-Koyanagi Harada disease (VKH). The lymphocytes from PBMC with VKH disease patients proliferate against tyrosinase family proteins. These results suggest that tyrosinase family proteins are antigens specific to VKH.In this project, we further confirmed these results and studied the immune reactions involved in VKH.To clarify the development and differentiation of autoreactive T cells in VKH, we are now making the transgenic Lewis rats expressing tyrosinase. Lewis rats lacks the tyrosinase, but are sensitive to the various kind of autoimmune disease. The Lewis rats that express tyrosinase in different organs and periods will be effective to study the central and peripheral tolerance against autoantigens.We are planing to make the transgenic rats that will express tyrosinase under the promoter of arrestin for retina specific expression, β-actin for ubiquitous expression and tyrosinase for melanocyte. We are now making the siblings of the rats bearing the transgene.