Molecular and Cellular Regulation of Tolerance

描述（由申请人提供）：这是一份继续资助一个项目的提案，该项目涉及诱导和维持免疫系统无反应性和耐受性的分子机制。三位研究者一致认为，耐受性是一个复杂的过程，在这个过程中，免疫细胞的固有反应以及与它们的解剖微环境的相互作用，在决定对自身和病原体相关抗原的反应性方面起着关键作用。为了与计划项目的总体主题保持一致，本次更新中提出的项目将考虑免疫系统相互作用性质背景下耐受的机制方面。在上一个资助期内，该项目的个别研究人员所取得的成就包括实验模型的设计和表征，这些模型现在可以进行有意义的机制分析。这些旨在提供将继续连接三个项目的方法和见解，从而促进协同作用并增加单个实验室进展的科学范围。Mark Greene博士已被该计划的新成员Yongwon Choi博士取代。Choi博士将研究TRANCE在外周T细胞稳态和对内源性抗原无反应性中的作用。行政核心将提供预算监督、手稿编写和进度报告的秘书支助以及安排调查员会议和顾问旅行安排的后勤支助。这三个实验室过去和未来的整合将在一定程度上提高科学质量和生产力，其进步将超过单个实验室的总和。

DESCRIPTION (provided by applicant): This is a proposal to continue funding for a Program to study the molecular mechanisms involved in the induction and maintenance of immune system unresponsiveness and tolerance. Three investigators are unified by the common theme that tolerance is a complex process in which the inherent responsiveness of immune cells, as well as interactions with their anatomical microenvironment, play pivotal roles in determining responsiveness to self- and pathogen-associated antigens. In keeping with the overall theme of the Program Project, the projects proposed in this renewal will consider mechanistic aspects of tolerance in the context of the interactive nature of the immune system. Accomplishments by the individual investigators in this Program during the last funding period include the design and characterization of experimental models that are now amenable to meaningful mechanistic analysis. These are intended to provide methodologies and insights that will continue to bridge the three projects, thereby facilitating synergy and increased scientific scope to the progress of the individual laboratories. Dr. Mark Greene has been replaced by a new member of the Program, Dr. Yongwon Choi. Dr. Choi will study the role of TRANCE in peripheral T cell homeostasis and unresponsiveness to endogenous antigen. An administrative core will provide budget oversight, secretarial support for manuscript preparation and progress reports, as well as logistical support for scheduling investigator meetings and travel arrangements of consultants. The past and future integration of the three laboratories will enhance the scientific quality and productivity to a degree that results in progress that will be greater than the sum of the individual laboratories.