T LMPHOCYTE MEMORY

描述（改编自申请人的摘要）：此特别强调 研究职业奖（SERCA）申请由兽医提交， 部分完成了免疫学系的博士课程， 哈佛大学艺术与科学研究生院。 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 免疫治疗剂，特别是与癌症相关的免疫治疗剂。 拟议 研究将使用细胞和分子技术来阐明 需要诱导和维持记忆性CD 4 + T淋巴细胞。 深入了解这些因素对人类和动物都很重要 健康，因为定义用于存储器单元生成的必要元素将 允许开发新的免疫策略， 传染病，以及更有效的工程 肿瘤疫苗 这项拟议中的研究将利用表达一种 特异性针对源自以下的肽的转基因T细胞受体（TCR） 卵清蛋白（OVA）。 具体而言，该项目的目标是明确地 表征表型、细胞因子产生和基因表达 与体内记忆细胞的存活和凋亡相关;以确定 抗原的性质，抗原呈递介导的共刺激， 细胞或细胞外基质分子，以及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OVA的DNA构建体，以及鉴定为 T细胞记忆的正调节因子，以在体内诱导功能性记忆; 并开发疫苗来预防 表达OVA的肿瘤。 本研究项目将在 哈佛医学院病理学教授Abul Abbas博士的指导 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.