T CELL GENE EXPRESSION AND TRAFFICING IN MURINE EAE

这名候选人加入了免疫学系， 1986年在韦恩州立大学学习微生物学， 有限韦恩州立大学在神经免疫学方面特别强 research. 这位候选人很快抓住了这个机会， 开发了一个旨在分析T细胞受体基因的研究项目， 表达以及致脑炎细胞的体内运输。 小鼠实验性自身免疫性脑脊髓炎（EAE）模型。 的一部分 这项贩卖人口研究目前由美国国立卫生研究院资助。 T细胞的研究 受体异质性目前部分由来自 国家多发性硬化症协会。 此外，重叠 申请正在NIH审查中。 的直接目标 研究计划是使用T细胞表面抗原作为遗传标记， 遵循致脑炎细胞的体内运输， EAE的发展。 具体而言，髓鞘碱性蛋白（MBP）特异性 将供体Thy-1.2+供体T细胞注射到初始Thy-1.1+供体T细胞中。 受惠人士 供体细胞在小鼠中枢神经系统和淋巴组织中的命运 接受者将通过Thy-1标记进行跟踪， 用单克隆抗Thy-1.2抗体检测。 这种方法 对于研究效应细胞机制尤其重要， 在疾病的自发复发阶段。 稳定的遗传 与放射性同位素标记的细胞不同，标记物可以在很长一段时间内被追踪 时间了 最近，候选人的实验室发现， 细胞转移受体的额外抗原攻击可导致 许多公认的“耐药”小鼠品系中的疾病发展， C57 BI/6和BALB/C。 这一实验系统开辟了新的途径， 研究EAE诱导易感性的遗传基础。 一 方法是通过以下方式检查T细胞受体（TCR）基因的使用情况： 这两种菌株的致脑炎细胞。 有限的概念 TCR基因使用的异质性带来了希望， 自身免疫性疾病可以通过TCR本身的操作来实现。 这将是非常重要的，以证实这些发现在额外的小鼠 PL和B10.PL以外的菌株，特别是在正常 对疾病诱导有抵抗力。 最终，这些关于疾病的知识 将利用耐药性来设计治疗人类的方法， 脱髓鞘疾病 这项研究计划既具有挑战性， 奖励授予RCDA将使候选人能够更多地 积极追求该计划的目标，并促进更密切的合作。 与神经免疫学专家的互动内外 部门 正如申请书中所指出的，候选人具有充分的 系和学校的支持。

This candidate joined the faculty of Department of Immunology and Microbiology at Wayne State University in 1986 after six years at Merck & Co. Wayne State University is particularly strong in Neuroimmunology research. The candidate quickly seized the opportunity and had since developed a research program aiming at analyzing the T cell receptor gene expression as well as in vivo trafficking of encephalitogenic cells in the murine experimental autoimmune encephalomyelitis (EAE) model. A part of the trafficking study is currently funded by NIH. The study on T cell receptor heterogeneity is currently partly funded by a grant from the National Multiple Sclerosis Society. In addition, an overlapping application is under review at NIH. The immediate objective of the research program is to use a T cell surface antigen as a genetic marker to follow the in vivo trafficking of encephalitogenic cells leading to the development of EAE. Specifically, myelin basic protein (MBP)-specific donor Thy-1.2+ donor T cells will be injected into naive Thy-1.1+ recipients. The fate of the donor cells in the CNS and lymphoid tissues of the recipients will be followed by virtue of the Thy-1 marker which can be detected with monoclonal anti-Thy-1.2 antibodies. This approach is especially important for the investigation of the effector cell mechanisms in the spontaneously relapsing phase of the disease. The stable genetic marker, unlike radioisotope-labeled cells, can be traced over a long period of time. Recently, the candidate's laboratory made the discovery that additional antigenic challenge of cell transfer recipients can lead to disease development in many reputed 'resistant' strains of mice such as C57BI/6 and BALB/C. This experimental system opens up new avenues for studying the genetic basis of susceptibility to EAE induction. One approach is to examine the T cell receptor (TCR) gene usage by encephalitogenic cells from these two strains. The concept of limited heterogeneity in TCR gene usage has raised hope that perhaps modulation of autoimmune diseases can be achieved through manipulation of the TCR itself. It will be very important to confirm these findings in additional mouse strains other than PL and B10.PL, especially in mice that are normally resistant to disease induction. Eventually, this knowledge of disease resistance will be utilized to design therapeutic approaches to human demyelinating diseases. This research program is both challenging and rewarding. The award of a RCDA will enable the candidate to more aggressively pursue the objectives of the program and to foster closer interactions with neuroimmunology experts within and outside of the Department. As noted in the application, the candidate has the full support of the Department and the School.