Regulation of T Cells by the Cytokines IL-7 and IL-15

细胞因子 IL-7 和 IL-15 对 T 细胞的调节

• 批准号: 6833547
• 负责人: Kimberly D. Klonowski
• 金额: $ 4.99万
• 依托单位: UNIVERSITY OF CONNECTICUT SCH OF MED/DNT
• 依托单位国家: 美国
• 财政年份: 2003
• 资助国家: 美国
• 起止时间: 2003-01-01 至 2005-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6833547
• 关键词: Regulation; Cells; Cytokines; IL; 15

18. GOALS FOR FELLOWSHIP TRAINING AND CAREER The training goals for my fellowship are to become more knowledgeable in basic T cell immunology, to learn and apply current cellular based immunological methods, and to gain the confidence and knowledge to develop insightful and novel e3periments independently. My previous research experience involved using molecular techniques to observe gene rearrangements and protein/gene expression in B cells. The project proposed in my fellowship provides the opportunity to analyze T cells in a cellular based context and better understand which factor(s) are integral in the generation of memory T cells in vivo. At the conclusion of my fellowship, I hope to be able to mesh together my previous molecular immunology experience with the cellular based applications to independently assess various regulators of memory T cell development. 19. NAME AND DEGREE(S) Leo Lefrancois_ Ph.D. 20. POSITION/RANK Professor of Medicine 21. RESEARCH INTERESTS/AREAS T Cell Memory 22. DESCRIPTION (Do not exceed space provided) Memory T cells are long-lived T cells which have previously encountered antigen and are poised for rapid response upon a secondary challenge. To date, the factor(s) involved in generating and maintaining the CD8 memory T cell pool remains an enigma. IL-7 is a well documented cytokine important for survival of CDS+T cells. Further, IL-15, a related cytokine, is also believed to be partially responsible for memory T cell development. The objective of this proposal is to evaluate the roles the two cytokines on memory T cell development and survival. To test whether IL-7 receptor (IL-7R) expression correlates with the generation of memory T cells, TCR transgenic IL-7Rtx h_and IL-7R(_ =¿expressing activated T cells will be transferred into normal mice. Donor cell attrition and IL-7R expression will be monitored over time. Blocking experiments using an anti-lL7Rt_ mAb will pinpoint the stage at which IL-7 is essential for memory T cell generation. To look at the effects of both IL-7 and IL-15 on memory T cell development, memory T cells will be transferred into IL-15-/- mice followed by anti-IL7Rct treatment. Together, these experiments will address the basic requirements for memory T cell development and may result in numerous clinical applications including augmenting vaccine efficacy. PHS 416-1 (Rev. 12198) Form Page 2 BB CC Individual NRSA Application Table of Contents ========================================Section End===========================================

18.奖学金的培训和职业目标我的奖学金的培训目标是更多地了解基础T细胞免疫学，学习和应用当前基于细胞的免疫学方法，并获得独立开发有洞察力和新颖性的实验的信心和知识。我之前的研究经验涉及使用分子技术观察B细胞的基因重排和蛋白质/基因表达。我在奖学金中提出的这个项目提供了在基于细胞的背景下分析T细胞的机会，并更好地了解在体内产生记忆T细胞的过程中哪个因素(S)是不可或缺的。在我的奖学金结束时，我希望能够将我以前的分子免疫学经验与基于细胞的应用相结合，以独立评估记忆T细胞发育的各种调节因素。19.姓名及学位(S)Leo Lefrancois_Ph.D.20.医学教授职位/职级研究兴趣/领域T细胞存储器22.说明(不超过所提供的空间)记忆T细胞是长寿的T细胞，它以前遇到过抗原，并准备好在二次挑战时做出快速反应。到目前为止，参与产生和维持CD8记忆T细胞池的因素(S)仍然是一个谜。IL-7是一种对CDS+T细胞的存活起重要作用的细胞因子。此外，IL-15，一种相关的细胞因子，也被认为是记忆T细胞发育的部分原因。本研究的目的是评估这两种细胞因子在记忆T细胞发育和存活中的作用。为了检测IL-7受体(IL-7R)的表达是否与记忆T细胞的生成有关，将TCR转基因的IL-7Rtx h_1和IL-7R(_=？)表达的活化T细胞转移到正常小鼠体内。随着时间的推移，将监测供体细胞的磨损和IL-7R的表达。使用抗lL7Rt_mAb的阻断实验将确定IL-7对记忆T细胞生成至关重要的阶段。为了观察IL-7和IL-15对记忆T细胞发育的影响，我们将记忆T细胞转移到IL-15-/-小鼠体内，然后进行抗IL-7Rct治疗。总之，这些实验将解决记忆T细胞发育的基本要求，并可能导致许多临床应用，包括增强疫苗效力。PHS 416-1(12198版)表第2页BB CC个人非RSA申请目录========================================Section End===========================================