CD4+ T Cell Receptors in Leishmaniasis

效应免疫主要由细胞因子介导，细胞因子是先天和分化的适应性T细胞的产物， 协调宿主防御和免疫病理学。免疫学的许多研究都集中在 淋巴器官或在体外分化期间。目前的兴趣越来越集中在周边 组织，效应细胞在其中执行其功能。使用具有敲入结构的小鼠， 通过记录细胞因子转录本，我们发现初始辅助性T细胞，当极化以表达特定细胞因子时， 维持IL-4和IFN-γ转录物在细胞中处于非翻译状态，我们将其定义为“定位”。 重新激活导致之前转录的信息的快速翻译，促进快速和灵活的翻译。 应答该提案试图定义正常幼稚T细胞的引发在多大程度上建立了免疫应答。 在细胞因子转录水平上的这种“平衡”效应状态;研究有助于 维持“平衡”状态;并使用充分表征的鼠寄生虫感染模型-包括 巴西日本圆线虫和硕大利什曼原虫-以确定体内是否存在相关途径。 该提案将使用各种转基因小鼠以及分子和生化检测 为了确定分化T细胞的过程是否被支架化到更普通的细胞上， 协调翻译与蛋白质分泌水平波动的途径。在幼稚和 将分化的辅助T细胞与驻留在组织中的效应细胞群进行比较， 包括NK细胞、NK T细胞和嗜酸性粒细胞。这样的分析可以使广泛的比较之间 不同的细胞类型激活IFN-γ基因，IL-4基因，或两种基因，可能揭示 核心遗传程序与免疫系统中的效应子功能密切相关。

Effector immunity is mediated largely by cytokines, products of innate and differentiated adaptive T cells that orchestrate both host defense and immunopathology. Much research in immunology has focused on cells in lymphoid organs or during in vitro differentiation. Current interest has increasingly focusing on peripheral tissues, where effector cells carry out their functions. Using mice with knockin constructs that faithfully record cytokine transcripts, we find that naive helper T cells, when polarized to express specific cytokines, maintain IL-4 and IFN-gamma transcripts in an untranslated state in the cell, which we define as 'poised'. Reactivation leads to rapid translation of the previously transcribed message, facilitating rapid and flexible responses. This proposal seeks to define the extent to which priming of normal naive T cells establishes such a 'poised' effector state at the level of cytokine transcripts; to investigate mechanisms that contribute to maintaining the 'poised' state; and to use well-characterized murine parasite infection models - including Nippostrongylus brasiliensis and Leishmania major - to establish whether the relevant pathways exist in vivo. The proposal will use a variety of genetically modified mice together with molecular and biochemical assays to establish whether the process used by differentiating T cells is scaffolded onto more general cellular pathways for coordinating translation with fluctuating levels of protein secretion. Findings made in naive and differentiated helper T cells will be compared with effector cell populations that are resident in tissues, including NK cells, NK T cells and eosinophils. Such analysis may allow broad comparisons between different cell types that activate the IFN-gamma gene, the IL-4 gene, or both genes, potentially revealing core genetic programs linked intimately with effector function in the immune system.