Molecular and Cellular Regulation of Tolerance

描述（由申请人提供）：这是一项继续资助一项计划的提案，该计划旨在研究诱导和维持免疫系统无反应性和耐受性的分子机制。三位研究人员通过共同的主题统一起来，即耐受性是一个复杂的过程，其中免疫细胞的固有反应性以及与其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发挥着关键作用。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在免疫系统相互作用的背景下考虑耐受性的机制方面。在上一个资助期内，该计划的个人研究人员取得的成就包括设计和表征实验模型，这些模型现在可以进行有意义的机理分析。这些建议旨在提供方法和见解，继续将这三个项目联系起来，从而促进协同作用，并扩大各个实验室进展的科学范围。Mark格林博士已被该方案的新成员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。一个行政核心将提供预算监督、文稿编写和进度报告的秘书处支助，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将来的整合将提高科学质量和生产力，其结果是取得的进展将大于单个实验室的总和。

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 Mark Greene has been replaced by a new member of the Program, Dr.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.