Imprinting of Lung-Resident T Cell Memory

肺驻留 T 细胞记忆的印记

• 批准号: 8817929
• 负责人: JACOB E KOHLMEIER
• 金额: $ 38.79万
• 依托单位: EMORY UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-12-01 至 2019-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8817929
• 关键词: Animal Model; Antigens; Automobile Driving; CD8B1 gene; CXCL10 gene; CXCR6 gene; Cell Adhesion Molecules; Cells; Cellular Immunity; Data; Development; Future; Generations; Genetic; Goals; Health; Human; Immunity; Infection; Influenza; Interferons; Kinetics; Lung; Lymphoid Tissue; Maintenance; Mediating; Memory; Mycobacterium tuberculosis; Parainfluenza; Pattern; Peripheral; Population; Positioning Attribute; Production; Respiratory Tract Infections; Respiratory physiology; Role; Route; Severity of illness; Site; Skin; Structure of parenchyma of lung; T cell differentiation; T memory cell; T-Lymphocyte; Testing; Time; Tissues; Vaccination; Vaccine Design; Viral; Viral Load result; Virus; chemokine; chemokine receptor; clinically relevant; cytokine; global health; immunopathology; imprint; improved; pathogen; peripheral blood; programs; protective effect; protective efficacy; public health relevance; receptor; reproductive; respiratory; vaccine development; vaccinology

DESCRIPTION (provided by applicant): The lung is a common portal of pathogen entry, and respiratory pathogen such as influenza and Mycobacterium tuberculosis are major global health problems. Thus, a major challenge of pulmonary vaccinology is to develop an approach that will provide long-lasting and durable immunity in the lung. One approach to this problem is the development of vaccines designed to promote the generation of lung-resident T cell memory. In animal models and human studies, memory T cells have been shown to significantly reduce viral loads after influenza challenge, leading to faster viral clearance and decreased disease severity. A key finding from these and other studies was that the protective efficacy of memory T cells directly correlated with the number of memory T cells present in the lung at the time of influenza challenge; as the number memory T cells in the lung declined, so did protection from pathogen challenge. Therefore, generating memory T cells that reside in the lung parenchyma and lung airways is a promising strategy to enhance cellular immunty to influenza or other respiratory pathogens. However, we still lack a basic understanding of how to generate and maintain tissue-resident memory T cells at the site of infection (the lung) where they are uniquely positioned to rapidly respond to a respiratory infection. Furthermore, we do not know the effector mechanisms that lung resident-memory cells use to provide protecitive immuniy. To improve cellular immunity against respiratory pathogens we must first acquire a better understanding of the mechanism(s) that underlie the generation, maintenance, and recall of tissue-resident memory T cells in the lung airways and lung parenchyma. This is the goal of the current proposal.

描述（由申请人提供）：肺是病原体进入的一个常见门户，呼吸道病原体（如流感和结核分枝杆菌）是全球主要的健康问题。因此，肺疫苗学的主要挑战是开发一种方法，该方法将在肺中提供持久耐用的免疫力。解决这个问题的一种方法是开发旨在促进肺部T细胞记忆产生的疫苗。在动物模型和人类研究中，记忆T细胞已被证明可显着降低流感挑战后的病毒载量，从而更快地导致病毒清除率和疾病的严重程度降低。这些研究和其他研究的一个关键发现是，记忆T细胞的保护功效与流感挑战时肺中存在的记忆T细胞的数量直接相关。随着肺中的数量记忆T细胞的数量下降，免受病原体挑战的保护也会下降。因此，产生驻留在肺实质和肺气道中的记忆T细胞是增强对流感或其他呼吸道病原体的细胞免疫的有前途的策略。但是，我们仍然缺乏对如何在感染部位（肺）产生和维持组织居住的记忆T细胞的基本理解，在那里它们具有唯一位置以快速响应呼吸道感染。此外，我们不知道肺常驻内存细胞用来提供蛋白质免疫的效应机制。为了改善对呼吸道病原体的细胞免疫力，我们必须首先了解对机制的理解，这些机制是肺气道和肺实质中组织居住记忆T细胞的产生，维持和回忆的基础。这是当前建议的目标。