IMMUNE DEVIATION INDUCED BY GENE VACCINATION--APPLICATIONS TO ARTHRITIS

类风湿性关节炎是一种慢性炎症性疾病，主要影响 周围滑膜关节。类风湿性关节炎的发病机制 似乎是多因素的，包括遗传易感性， 出生后事件中的免疫成熟，反复暴露在环境中 抗原和放大的细胞因子网络使炎症永久化。 致病抗原可能直接在免疫部位表达。 攻击Pr与自然产生的抗原表位发生交叉反应 那家大麻店。我们假设，刺激T细胞的一个子集 通过操纵关节特异性抗原来分泌IL4或IL10 抗原呈递环境可能会消灭疾病。在我们的预赛中 实验我们开发了一种系统，通过这个系统，有限的表位 通过注射到真皮或肌肉组织中的质粒DNA来表达 老鼠。T细胞对这些抗原的反应是另外有偏见的 不仅由表位表达，而且还由不同的共刺激 在附近表达的分子。这种提供不同功能的方法 参与启动免疫反应的元素创建了一个局部 免疫窗口。在我们的实验室里，我们还开发了一种独特的 将抗原呈递限制为CD1的异构体的系统。我们的目标是1) 评估不同共刺激分子对偏离 对胶原的免疫反应2)确定是否提供额外的抗原性 伴侣或共价连接抗原伴侣可增强免疫力 偏差3)评估CD1D1限制性反应的调节作用 在胶原蛋白诱导的关节炎中，以及4)确定这些发现是否来自我们的 胶原蛋白诱导的关节炎模型中的三种策略适用于 转基因小鼠自发发育的不同模型 关节炎。

Rheumatoid arthritis is a chronic inflammatory disease primary affecting peripheral synovial joints. The etiopathogenesis of rheumatoid arthritis appears to be multi-factorial, including hereditary susceptibility, postnatal events in immune maturation, repeated exposure to environmental antigens and amplifying cytokine networks that perpetuate inflammation. The causative antigens may be directly expressed at the site of immune attack pr be cross reactive with antigenic epitopes naturally occurring in the joint. We postulate that stimulating a subset of T cells that respond to a joint specific antigen to secrete IL4 or IL10 by manipulating the antigen presenting environment may abrogate disease. In our preliminary experiments we have developed a system whereby limited epitopes are expressed by plasmid DNA injected into the dermis or muscle tissues of mice. The T cell response to these antigens is additionally biased not only by the epitope expressed, but also by different co-stimulatory molecules expressed in the vicinity. This method of providing different elements involved in priming of an immune response creates a local immunologic window. In our laboratory we have also developed a unique system to limit antigen presentation to an isoform of CD1. We aim to 1) assess the effects of different co-stimulatory molecules on deviating the immune response to collagen 2) determine if providing additional antigenic chaperones or covalently linking the antigen chaperones potentiates immune deviation 3) evaluate a regulatory role for the CD1D1 restricted responses in collagen induced arthritis and 4) determine if the findings form our three strategies in the collagen induced arthritis model apply to a different transgenic mouse model in which the mice spontaneously develop arthritis.