The role of autophagy in T cell immune response

自噬在 T 细胞免疫反应中的作用

基本信息

批准号：
8286886
负责人：
IVICA ARSOV
金额：
$ 11.8万
依托单位：
YORK COLLEGE
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：
2009-08-01 至 2015-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8286886
关键词：
Ablation Address Aging Animals Antigens Apoptosis Applications Grants Area Asses Autophagocytosis B-Lymphocytes Biochemical Biological Assay CD8B1 gene Cell Death Cell physiology Cells Collaborations Dendritic Cells Development Digestion Flow Cytometry Fluorescence Funding Genes Grant Hematopoiesis Homeostasis Hospitals Image Immune Immune response Immune system Immunization Knockout Mice Lymphocyte Malignant Neoplasms Manuscripts Memory Methods Mouse Strains Mus Natural Immunity Neurodegenerative Disorders Ovalbumin Play Process Productivity Progress Reports Proteins Publications Publishing Reporter Research Role Starvation T cell response T memory cell T-Cell Activation T-Cell Development T-Lymphocyte Western Blotting Wild Type Mouse Writing adaptive immunity base cell mediated immune response immune activation improved in vivo insight knockout animal macrophage novel pathogen programs public health relevance research study response senescence

项目摘要

DESCRIPTION (provided by applicant): Autophagy is an evolutionarily conserved process of cellular self-digestion, primarily used to maintain cellular energy homeostasis during starvation. In recent years, the new evidence is emerging implicating this process in development and differentiation, apoptosis, cancer, aging and senescence, and the immune response. In this proposal, we will utilize several strains of genetically modified mice to understand the role of autophagy in the T cell-mediated immune response. One group of mice will be used to study the induction of autophagic activity in different immune cells, such as lymphocytes, macrophages, and dendritic cells, under normal conditions and following immunization with an antigen by flow cytometry and biochemical assays. This group of mice contains several trangenic strains expressing green fluorescence protein-tagged versions of different autophagic proteins, such as Beclin 1, LC3, and Atg5. These reporter mice will allow us to determine a constitutive as well as antigen-induced autophagy in immune cells. To determine the function of autophagy in the T cell immune response, we will use mice deficient in autophagy essential protein Atg7. These mice will be immunized, and the T cell immune response to antigen in the absence of autophagy analyzed using flow cytometry and fuctional assays. This approach should provide a novel insight into the role of autophagy in the adaptive immune system. PUBLIC HEALTH RELEVANCE: In this proposal, we will characterize the role of autophagy in the adaptive immune system. This study should improve our understanding of the adaptive immunity, as well as of the role of autophagy in the initiation of the T cell immune activation and T cell memory, which are essential for the body's defense against different pathogens.

描述（由申请人提供）：自噬是一种进化上保守的细胞自我消化过程，主要用于在饥饿期间维持细胞能量稳态。近年来，不断出现的新证据表明这一过程与发育和分化、细胞凋亡、癌症、衰老和衰老以及免疫反应有关。在本提案中，我们将利用几种转基因小鼠品系来了解自噬在 T 细胞介导的免疫反应中的作用。一组小鼠将用于研究正常条件下和抗原免疫后不同免疫细胞（例如淋巴细胞、巨噬细胞和树突状细胞）中自噬活性的诱导，通过流式细胞术和生化测定。这组小鼠含有几种表达绿色荧光蛋白标记版本的不同自噬蛋白的转基因品系，例如 Beclin 1、LC3 和 Atg5。这些报告小鼠将使我们能够确定免疫细胞中的组成型自噬以及抗原诱导的自噬。为了确定自噬在 T 细胞免疫反应中的功能，我们将使用自噬必需蛋白 Atg7 缺陷的小鼠。这些小鼠将被免疫，并使用流式细胞术和功能测定分析在没有自噬的情况下 T 细胞对抗原的免疫反应。这种方法应该为自噬在适应性免疫系统中的作用提供新的见解。公共健康相关性：在本提案中，我们将描述自噬在适应性免疫系统中的作用。这项研究应该提高我们对适应性免疫以及自噬在 T 细胞免疫激活和 T 细胞记忆启动中的作用的理解，这对于人体防御不同病原体至关重要。