T LYMPHOCYTE ACTIVATION IN SYSTEMIC RHEUMATIC DISEASE

这份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具有广泛的教育经验， 以此作为独立调查员的职业生涯 的 课程计划包括微生物学的正式课程，沿着 该研究项目旨在为P.I.密集 实验室研究训练。 本项目的研究重点是对 人类T淋巴细胞活化的四种途径。 据了解，T 淋巴细胞可以用抗CD2的单克隆抗体活化， CD3、CD28和CD69通路。 相对而言， 比较这些途径，但似乎确实存在差异， 他们之间 通过这些途径的淋巴细胞活化将是 研究，包括比较分析细胞因子mRNA的生产， PCR，胸苷掺入法增殖反应，蛋白酪氨酸 通过免疫印迹在细胞底物中的激酶磷酸化，和 通过北方分析测定原癌基因mRNA的产生。 独特 将进一步表征磷酸酪氨酸蛋白。亚群t 淋巴细胞如CD4+、CD8+、CD45RA+和CD45RO+将在 以确定这些子集中的差异。 这些信息将 然后作为研究全身淋巴细胞活化的基线， 风湿病 系统性红斑狼疮和类风湿关节炎 将作为模型，因为这两种疾病都涉及到 T淋巴细胞功能异常。 本研究的目的是作为一种培训工具， 私家侦探成为一名独立调查员 人们希望 这些研究将有助于更好地了解正常T细胞 激活沿着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 作为私人侦探进一步研究的基础风湿性 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.