T LYMPHOCYTE ACTIVATION IN SYSTEMIC RHEUMATIC DISEASE

这份关于医生科学家奖的提案概述了一项培训计划 旨在为私家侦探提供广泛的教育体验 以此为基础建立独立调查员的职业生涯。这个 课程计划包括微生物学方面的正式课程，以及 研究项目，旨在为私家侦探提供密集的 在板凳研究方面的培训。 本课题的研究重点集中在两种语言的比较分析上 人类T淋巴细胞活化的四条途径。众所周知，T 淋巴细胞可以用抗CD2的单抗激活， CD3、CD28和CD69通路。已经完成的工作相对较少 比较这些途径，但似乎确实存在差异 在他们之间。通过这些途径激活的淋巴细胞将是 研究，包括对细胞因子mRNA产生的比较分析 聚合酶链式反应、胸腺嘧啶核苷掺入增殖反应、蛋白酪氨酸 免疫印迹法检测细胞底物中的激酶磷酸化，以及 Northern分析确定原癌基因的mRNA产量。独一无二 磷酸酪氨酸蛋白将被进一步鉴定。T的子集 淋巴细胞，如CD4，CD8，CD45RA和CD45RO将在 以确定这些子集中的差异。此信息将 以此为基线研究系统性红斑狼疮患者的淋巴细胞活化 风湿病。系统性红斑狼疮与类风湿关节炎 将作为模型，因为这两种疾病都被牵连为 有T淋巴细胞功能异常。 本研究的目的是作为一种培训工具，以允许 私家侦探要发展成独立的调查员。人们希望， 这些研究将有助于更好地理解正常T细胞 激活，并可能导致进一步深入了解 风湿病的发病机制。此外，这项工作应该服务于 作为P.I.进一步研究风湿性疾病的基础 疾病。

This proposal for a Physician scientist Award outlines a training program designed to provide the P.I. with a broad based educational experience upon which to establish a career as an independent investigator. The program plan consists of formal coursework in Microbiology along with a research project which is designed to provide the P.I. with intensive training in bench research. The research focus of this project centers on a comparative analysis of four pathways of human T lymphocyte activation. It is known that T lymphocytes can be activated using monoclonal antibodies against the CD2, CD3, CD28, and CD69 pathways. Relatively little work has been done comparing these pathways, but it appears that differences do exist between them. Lymphocyte activation through these pathways will be studied, including a comparative analysis of cytokine mRNA production by PCR, proliferative response by thymidine incorporation, protein tyrosine kinase phosphorylation in cellular substrates by immunoblotting, and proto-oncogene mRNA production determined by Northern analysis. Unique phosphotyrosine proteins will be further characterized. Subsets of T lymphocytes such as CD4+, CD8+, CD45RA+, and CD45RO+ will be examined in order to determine differences in these subsets. This information will then serve as a baseline to study lymphocyte activation in systemic rheumatic disease. Systemic lupus erythematosus and rheumatoid arthritis will serve as models as both of these disorders have been implicated as having abnormalities of T lymphocyte function. It is the purpose of this study to serve as a training vehicle to allow the P.I. to develop into an independent investigator. It is hoped that these studies will lead to a better understanding of normal T cell activation along with potentially leading to further insight into the mechanisms of rheumatic disease. Additionally, this work should serve as a foundation leading to further research by the P.I. in rheumatic disease.