The role of autophagy in T cell immune response

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，新的证据表明这一过程与发育和分化、细胞凋亡、癌症、衰老和免疫反应有关。在这个提议中，我们将利用几种转基因小鼠来了解自噬在T细胞介导的免疫反应中的作用。一组小鼠将用于研究在正常条件下和在用抗原免疫后通过流式细胞术和生物化学测定法诱导不同免疫细胞（例如淋巴细胞、巨噬细胞和树突细胞）中的自噬活性。这组小鼠含有几种转基因菌株，它们表达不同自噬蛋白的绿色荧光蛋白标记版本，如Beclin 1、LC 3和Atg 5。这些报告小鼠将使我们能够确定免疫细胞中的组成性以及抗原诱导的自噬。为了确定自噬在T细胞免疫应答中的功能，我们将使用自噬必需蛋白Atg 7缺陷的小鼠。将这些小鼠免疫，并且使用流式细胞术和功能测定分析在不存在自噬的情况下T细胞对抗原的免疫应答。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。 公共卫生相关性：在这项提案中，我们将描述自噬在适应性免疫系统中的作用。这项研究将提高我们对适应性免疫的理解，以及自噬在启动T细胞免疫激活和T细胞记忆中的作用，这对机体防御不同病原体至关重要。

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.