T LMPHOCYTE MEMORY

描述(改编自申请人的摘要)：本特别强调 研究职业奖(SERCA)的申请是由一名兽医提交的 已在华盛顿大学免疫学系完成了部分博士课程 哈佛大学文理研究生院。候选人的 长期的利益在于使用动物模型来开发和测试新的 免疫治疗学，特别是与癌症相关的。建议数 研究将使用细胞和分子技术来阐明 记忆性CD4+T淋巴细胞的诱导和维持要求。 了解这些因素对人类和动物都很重要 健康，因为定义用于存储单元生成的必要元素将 允许为广泛的阵列开发新的免疫策略 对传染病的研究，以及对工程的更有效 肿瘤疫苗。这项拟议的研究将利用小鼠表达一种 抗源多肽的转基因T细胞受体(TCR) 卵清蛋白(OVA)具体地说，这个项目的目标是明确地 表征基因的表型、细胞因子的产生和表达 与体内记忆细胞的存活和凋亡相关；确定 抗原的性质如何通过共刺激介导的抗原递呈 细胞或细胞外基质分子和细胞因子环境的影响 记忆性T细胞的诱导和存活；检测质粒的能力 编码卵子蛋白的DNA结构，以及其他被鉴定为 正调节T细胞记忆，在体内诱导功能性记忆； 并开发疫苗以预防沙门氏菌的生长 表达卵子的肿瘤。这项研究项目将在 哈佛医学院病理学教授阿布·阿巴斯博士的指导 和布里格姆妇女医院。

DESCRIPTION (Adapted from the applicant's abstract): This Special Emphasis Research Career Award (SERCA) application is submitted by a veterinarian who has partially completed a PhD program in the Division of Immunology at the Graduate School of Arts and Sciences at Harvard University. The candidate's long term interests lie in the use of animal models to develop and test new immunotherapeutics, particularly with relevance to cancer. The proposed research will use cellular and molecular techniques to elucidate the requirements for the induction and maintenance of memory CD4+ T lymphocytes. Gaining insight into these factors is important to both human and animal health, as defining the necessary elements for memory cell generation will allow for the development of novel immunization strategies for a wide array of infectious diseases, as well as for the engineering of more effective tumor vaccines. The proposed research will utilize mice expressing a transgenic T cell receptor (TCR) specific for a peptide derived from ovalbumin (OVA). Specifically, the aims of this project are to definitively characterize the phenotype, cytokine production, and expression of genes associated with survival and apoptosis in memory cells in vivo; to determine how the nature of the antigen, costimulation mediated by antigen-presenting cells or extracellular matrix molecules, and cytokine environment influence the induction and survival of memory T cells; to test the ability of plasmid DNA constructs encoding OVA, as well as other costimulators identified as positive regulators of T cell memory, to induce functional memory in vivo; and to develop vaccines for protecting against the outgrowth of OVA-expressing tumors. This research project will be conducted under the direction of Dr. Abul Abbas, Professor of Pathology, Harvard Medical School and Brigham and Women's Hospital.