Tissue Regulation of T Cell Function

项目摘要/摘要--总体 病原体感染引发局部炎症，从而导致先天效应细胞的涌入和精加工 趋化因子、细胞因子和其他可溶性介质。进入感染组织的T效应细胞遇到 与基础状态不同的组织环境，取决于病原体的类型 以及相应的先天炎症反应。效应器T细胞必须通过这个间质空间迁移 定位抗原提呈细胞和受感染的靶细胞，并接收效应器功能的激活信号， 病原体清除和组织记忆的建立。尽管这些复杂的框架 天然细胞、可溶性介质和组织结构之间的相互作用已经建立，效应器的能力 T细胞能够感知和解释不同的炎症环境以及对免疫功能的影响 人们对此知之甚少。然而，正是在感染的外周组织中，它们必须执行它们的效应器功能 用来清除病原体。在周围组织中，失调的炎症也会导致免疫 病理学；从自身免疫到心血管疾病。使用创新的工具进行原位调制和 小鼠皮肤和肺部免疫反应的可视化这个项目的目标是 洞察控制感染或感染的T细胞募集、迁移和激活的信号 皮肤和肺部发炎的组织。之前的资金周期已经确定了T细胞的新机制 效应器和组织记忆亚群的重新招募、间质迁移和定位。这项建议建立了 在炎症部位的这些分子检查点上，以确定来自固有细胞的外部信号如何 而组织微环境决定了效应性T细胞的位置和功能，以实现保护性免疫。 项目1.有效T细胞功能和组织修复的中性粒细胞反应的解决。金敏秀博士。 假设：中性粒细胞死亡不是被动的，而是从死亡中释放出特定的因子 中性粒细胞促进有效的T细胞激活和组织修复。 项目2：通过细胞因子/趋化因子依赖对炎症部位T细胞激活的空间优化 蜂窝集群。黛博拉·福厄尔医生。假设：外周T细胞激活发生在富含趋化因子的情况下 血管周围聚集成核并放大T细胞募集/激活，以有效清除病原体。 项目3.组织驻留记忆CD8+T细胞的形成、定位、运动和功能 流感感染。大卫·托帕姆博士。假设：特定的TRM子集占据不同的空间 呼吸道中的微环境在预防流感感染方面具有不同的功能。 项目4：T细胞迁移的机制。帕特里克·奥克斯医生。假设：不同免疫系统的迁移 细胞沿着单一的连续体存在，只是在粘附力和力产生的相对贡献上不同。 首页--期刊主要分类--期刊细介绍--期刊题录与文摘--期刊详细文摘内容

PROJECT SUMMARY/ABSTRACT – OVERALL Pathogen infection initiates local inflammation that leads to the influx of innate effector cells and elaboration of chemokines, cytokines and other soluble mediators. T effector cells entering the infected tissue encounter a tissue environment that has been differentially altered from the basal state depending on the type of pathogen and corresponding innate inflammatory response. Effector T cells must migrate through this interstitial space to locate antigen-presenting cells and infected target cells and receive activation signals for effector function, pathogen clearance and establishment of tissue memory. Although the framework of these complex interactions between innate cells, soluble mediators and tissue architecture is established, the ability of effector T cells to sense and interpret different inflammatory environments and the impact on immune function are poorly understood. Yet, it is within the infected peripheral tissues that they must execute their effector function for pathogen clearance. It is also within peripheral tissues where dysregulated inflammation leads to immune pathology; from autoimmune to cardio-vascular disease. Using innovative tools for in situ modulation and visualization of immune responses in the skin and lung of the mouse the goal of this Program Project is to gain insight into the signals that control T cell recruitment, migration and activation in infected or inflamed tissues of the skin and lung. The previous funding cycle has identified new mechanisms of T cell recruitment, interstitial migration, and positioning of effector and tissue memory subsets. This proposal builds on these molecular checkpoints at sites of inflammation to determine how external signals from innate cells and the tissue microenvironment shape the position and function of effector T cells for protective immunity. Project 1. Resolution of neutrophil response for effective T cell functions and tissue repair. Dr Minsoo Kim. Hypothesis: that neutrophil death is not passive, but rather, that the release of specific factors from dying neutrophils promotes effective T cell activation and tissue repair. Project 2. Spatial optimization of T cell activation at inflamed sites via cytokine/chemokine-dependent cellular clustering. Dr Deborah Fowell. Hypothesis: that peripheral T cell activation occurs in chemokine-rich peri-vascular clusters that nucleate and amplify T cell recruitment/activation for efficient pathogen clearance. Project 3. Formation, Positioning, Motility, and Function of Tissue Resident Memory CD8+ T cells After Influenza Infection. Dr David Topham. Hypothesis: specific TRM subsets occupy distinct spatial microenvironments in the airway that confer functional differences in protection against influenza infection. Project 4. Mechanics of T cell migration. Dr Patrick Oakes. Hypothesis: that migration of different immune cells lies along a single continuum, differing only in relative contributions of adhesion and force generation. Core A. Administrative, Fowell D.J.; Core B. Imaging, Kim M.; Core C. Reagents, Miller J.