Mechanisms of immune Failure in Chronic Infection: Hepatitis C as a Key Paradigm

慢性感染免疫失败的机制：丙型肝炎作为关键范例

基本信息

批准号：
8475539
负责人：
RAYMOND T CHUNG
金额：
$ 272.88万
依托单位：
MASSACHUSETTS GENERAL HOSPITAL
依托单位国家：
美国
项目类别：
财政年份：
2009
资助国家：
美国
起止时间：
2009-06-08 至 2014-05-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8475539
关键词：
Activities of Daily Living Address Antigen-Presenting Cells Area Biological Biology Blood Cells Cellular biology Centers for Disease Control and Prevention (U.S.)Chronic Cirrhosis Clinical Clinical Medicine Collaborations Communicable Diseases Cytomegalovirus Disease Progression Evolution Failure Genomics HIV Hepatitis C Hepatitis C virus Hepatocyte Hepatology Homing Human Human Herpesvirus 4 Immune Immune response Immune system Immunity Immunologics Immunology Infection Intervention Lead Libraries Liver Failure Malignant neoplasm of liver Molecular Biology Mycobacterium tuberculosis Outcome Play Population Program Development RNA Reagent Research Personnel Risk Role Signal Pathway Signal Transduction Sum Surface T-Lymphocyte Targeted Research Technology Therapeutic Therapeutic Intervention Tissues Vaccines Viral Viral Pathogenesis Viral Tumor Antigens Viremia Virus chronic liver disease cohort fitness global health improved insight intrahepatic man novel diagnostics novel therapeutics pathogen pressure programs prophylactic response viral RNA virology

项目摘要

The program comprises 7 major subthemes - 4 projects, 2 specific cores and one technical development program. The leader of each team has specific expertise in one area of clinical medicine, immunology, cell biology and/or molecular biology. Each on their own has made a significant contribution to the bigger picture of viral pathogenesis in hepatitis C. The key feature of this consortium is that these have been blended to create a scientific team which is more than the sum of its parts, as will be detailed below. Specifically we propose to:- 1. Define the role of the hepatocyte as a key player in innate and adaptive immune responses (Project 1 Chung) 2. Define the specific qualities of tissue homing T cell populations in relation to hepatitis C infection (Project 2, Klenerman). 3. Define the functional capacity of intrahepatic T cell populations in persistent infection (Project 3, Lauer/Wherry). 4. Define the impact of T cell selection pressure on viral sequence evolution and the fitness landscape (Project 4, Allen/Henn). 5. Create a panel of reagents to modulate the surface signaling platform of T cells and antigen presenting cells (Core C/Freeman). 6. Create a library of tissue and cells from well defined clinical cohorts for experimental use (Core D/Misradji). 7. Develop a platform technology to examine and modulate critical signaling pathways that limit the adaptive immune response (TDP/Haining).

该计划包括7个主要子主题-4个项目，2个特定核心和1个技术发展程序。每个团队的领导者在临床医学，免疫学，细胞的一个领域都有特定的专业知识生物学和/或分子生物学。每个人都为更大的情况做出了重大贡献丙型肝炎中病毒发病机理的作用。该财团的关键特征是这些财团已融合到创建一个科学团队，它不仅仅是其部分的总和，如下所示。具体而言，我们建议： - 1。将肝细胞的作用定义为先天和适应性免疫反应中的关键参与者（项目1 Chung） 2。定义与丙型肝炎感染有关的组织寄居T细胞群体的特定品质（Klenerman项目2）。 3。定义持续感染中肝内T细胞种群的功能能力（项目3， Lauer/Wherry）。 4。定义T细胞选择压力对病毒序列演化和适应性的影响景观（项目4，艾伦/亨恩）。 5。创建一组试剂，以调节T细胞和抗原的表面信号平台呈现细胞（核心C/Freeman）。 6。创建一个来自定义明确的临床同类群的组织和细胞库（核心） d/misradji）。 7。开发一种平台技术来检查和调节限制的关键信号通路自适应免疫反应（TDP/Haining）。