Manipulating collectivity and Niches for Developing CD8 Immunity

操纵集体和利基来发展 CD8 免疫力

基本信息

批准号：
9282416
负责人：
MATTHEW F KRUMMEL
金额：
$ 44.77万
依托单位：
UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
依托单位国家：
美国
项目类别：
财政年份：
2015
资助国家：
美国
起止时间：
2015-06-15 至 2020-05-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9282416
关键词：
Address Affinity Antigen Presentation Antigens Area Biological Assay CD8-Positive T-Lymphocytes CD8B1 gene Cell Communication Cells Clinical Clone Cells Collaborations Communication Competence Goals Health Hour Human Image Immune Immune response Immunity Immunization Immunoassay Immunology procedure In Situ Individual Influenza Influenza vaccination Knowledge Link Lung Maps Mediating Memory Molecular Monitor National Institute of Allergy and Infectious Disease Natural Killer Cells Nature Organ Outcome Peripheral Population Recruitment Activity Regimen Regulatory T-Lymphocyte Research Personnel Resolution Role Route Series Site Solid Specific qualifier value Synapses T-Cell Activation T-Cell Development T-Lymphocyte Testing Time Tissues Vaccination Viral Viral Vaccines Virus Work base cohort experimental study imaging approach imaging modality improved innovation interest lymph nodes member novel pathogen public health relevance response

项目摘要

DESCRIPTION (provided by applicant): What actually happens to responding T cells in the lymph node during vaccination? Specifically: What is the nature of the developing physical `niche' in which cells activate? Who are the members of this cohort and what are the critical temporal features that bridge two concurrent responses? We intend to discover the answers to these questions as a route to determining how to achieve solid CD8 T cell immunity to viruses. We will focus efforts both in lymph node and in the lung and the latter will access cutting-edge imaging approaches developed in our lab. We and others have recently used live imaging to demonstrate that T cell priming in the lymph node and reactivation in the lung take place under highly dynamic conditions that would appear to permit considerable mixing of ongoing responses. Our lab has established a series of cutting-edge imaging approaches including multiphoton-based cell-tracking and synapse-analysis, paired with our expertise in `classical' immunological assays, to study this `collective' activation; activation of multiple T cells that occupy the same reactive lymph node. A key finding that is corroborated by others is that there is a `Critical Differentiation Period' that coincides with individual activating T cell clones comig together into a T-T synapse-mediated contact. Based on our work and that of others in the field, we hypothesize that there are both natural and synthetic forms of cell- cell interactions that can be leveraged during elicitation of a CD8 response and that these will alter the outcome of a viral challenge. Through addressing this hypothesis, we aim to finally provide a rationale understanding of how immune cells co-activate and improving vaccination for CD8 responses.

描述（由适用提供）：在疫苗期间，淋巴结中的T细胞实际上发生了什么？具体来说：在哪种细胞激活的生理“利基市场”中的性质是什么？谁是该队列的成员，桥接两个并发响应的关键临时功能是什么？我们打算发现这些问题的答案，以确定如何实现对病毒的固体CD8 T细胞免疫。我们将把精力集中在淋巴结和肺部，后来将访问我们实验室中开发的尖端成像方法。我们和其他人最近使用实时成像来证明淋巴结中的T细胞启动和肺中的重新激活发生在高度动态的条件下，似乎可以考虑对正在进行的反应进行考虑。我们的实验室已经建立了一系列尖端的成像方法，包括基于多光子的细胞跟踪和突触分析，并与我们在“经典”免疫评估方面的专业知识相吻合，以研究这种“集体”激活；占据相同反应性淋巴结的多个T细胞的激活。其他人证实的一个关键发现是，存在一个“关键分化周期”，它与单个激活T细胞克隆的comig共同进入T-T突触介导的接触。根据我们的工作以及该领域的其他工作，我们假设在启发CD8响应时可以利用天然和合成形式的细胞 - 细胞相互作用形式，并且这些相互作用将改变病毒挑战的结果。通过解决这一假设，我们旨在最终提供对免疫小球如何共同激活和改善CD8反应疫苗接种的理由理解。