Apoptosis in the Generation of T-cell Memory

描述(申请人提供)：研究：这是一项研究计划，旨在研究细胞凋亡在T细胞记忆发育中的作用。感染后，T细胞经历快速克隆性扩增，导致抗原特异性T细胞的数量和频率增加。最初的扩增阶段之后很快就是收缩阶段(克隆性收缩)，超过90%的抗原特异性T细胞被消除。幸存的抗原特异性T细胞创造了记忆池，并提供了持久的保护，防止再次挑战。本文提出的研究旨在阐明细胞凋亡对发育中的抗原特异性T细胞记忆池的质量和功能的影响机制。特别是，我们的目标是：1)确定死亡受体介导的凋亡通路在记忆T细胞室的产生和动态平衡中的作用。2)检测Bcl2调控的线粒体依赖的细胞凋亡通路在抗原特异性T细胞记忆发育中的作用。3)探讨T细胞记忆产生过程中抗原介导的免疫反应中细胞增殖与细胞凋亡易感性的关系。这项拟议的研究将我们对T细胞功能的理解与当前关于细胞凋亡作用的想法结合在一起。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，并在劳伦斯·图尔卡博士的指导下于2003年获得宾夕法尼亚大学医学院博士学位。他的免疫学论文主要研究调节性T细胞的发育和功能。他目前是道格拉斯·格林博士实验室拉霍亚过敏和免疫学研究所(L1AI)的研究科学家。*环境：格林博士目前是LIAI细胞免疫学的负责人，被公认为免疫学和细胞凋亡领域的专家，有出色的出版记录。他在培训独立科学家方面有着良好的记录。LIAI在免疫学和分子细胞生物学领域都是国际公认的领导者，并为开展拟议的研究提供了良好的环境和必要的内部设施。

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.