Apoptosis in the Generation of T-cell Memory

描述（由申请人提供）：研究：这是一项研究提案，旨在检查细胞凋亡在T细胞记忆发展中的作用。感染后，T细胞经历快速克隆扩增，导致抗原特异性T细胞的数量增加和频率更高。初始扩增阶段之后是收缩阶段（克隆收缩），其中超过90%的抗原特异性T细胞被消除。存活的抗原特异性T细胞产生记忆池，并提供持久的保护免受再攻击。本文提出的研究旨在阐明细胞凋亡特异性地塑造发育中的抗原特异性T细胞记忆库的质量和功能的机制。具体而言，我们的目标是：1）确定死亡受体介导的凋亡途径在记忆T细胞区室的产生和稳态中的作用。2)检查Bcl-2调节的线粒体依赖性凋亡途径在抗原特异性T细胞记忆发展中的功能。3)检查在产生T细胞记忆的抗原介导的免疫应答期间增殖和对凋亡的易感性之间的关系。这项研究将我们对T细胞功能的理解与目前关于细胞凋亡作用的观点结合起来。候选人：本辛格博士以优异成绩毕业于宾夕法尼亚大学兽医学院，并获得博士学位。（2003年）在劳伦斯图尔卡博士的指导下从宾夕法尼亚大学医学院毕业。他的免疫学论文主要研究调节性T细胞的发育和功能。他目前是拉霍亚过敏和免疫学研究所（L1 AI）道格拉斯绿色博士实验室的研究科学家。* 环境：绿色博士目前是LIAI细胞免疫学的负责人，并被公认为免疫学和细胞凋亡领域的专家，拥有出色的出版记录。他在培养独立科学家方面有着良好的记录。LIAI是免疫学和分子细胞生物学领域的国际公认的领导者，并提供了一个良好的环境，必要的内部设施进行拟议的研究。

DESCRIPTION (provided by applicant): Research: This is a research proposal to examine the role of apoptosis in the development of T cell memory. Upon infection, T cells undergo rapid clonal expansion resulting in both increased numbers and higher frequency of antigen specific T cells. An initial expansion phase is quickly followed by a contraction phase (clonal contraction) where more than 90% of the antigen specific T cells are eliminated. The surviving antigen specific T cells create the memory pool and provide durable protection from re-challenge. The studies proposed herein are designed to elucidate the mechanisms by which apoptosis specifically shapes the quality and function of the developing antigen specific T cell memory pool. In particular, our aims are to: 1) Determine the role of death receptor mediated apoptosis pathways in the generation and homeostasis of the memory T cell compartment. 2) Examine the function of the Bcl-2 regulated, mitochondrial dependent apoptosis pathway in the development of the antigen specific T cell memory. 3) Examine the relationship between proliferation and susceptibility to apoptosis during antigen-mediated immune responses in the generation of T cell memory. The proposed research integrates our understanding of T cell function with current ideas regarding the role of apoptosis. Candidate: Dr. Bensinger graduated summa cum laude from the University of Pennsylvania School of Veterinary Medicine and received his Ph.D. (2003) from University of Pennsylvania School of Medicine under the mentorship of Dr. Laurence Turka. His thesis in immunology was focused on the development and function of regulatory T cells. He is currently a research scientist at the La Jolla Institute for Allergy and Immunology (L1AI) in the laboratory of Dr. Douglas Green. *Environment: Dr. Green is currently the head of cellular immunology at LIAI, and is recognized as an expert in both the fields of immunology and apoptosis with an outstanding publication record. He has a strong track record of training independent scientists. LIAI is an internationally recognized leader in both the fields of immunology and molecular cell biology and provides an excellent environment with the necessary in house facilities to conduct the proposed research.