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（由申请人提供）：在疫苗接种过程中，淋巴结中的 T 细胞实际上发生了什么？具体来说：细胞激活的发育中的物理“生态位”的性质是什么？该群体的成员有哪些？两个并发反应的关键时间特征是什么？我们打算找到这些问题的答案，作为确定如何实现对病毒的可靠 CD8 T 细胞免疫的途径，我们将集中精力在淋巴结和肺部，后者将进入。我们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 细胞启动和肺部的重新激活是在高度动态的条件下发生的，这似乎允许大量持续反应的混合。 - 边缘成像方法，包括基于多光子的细胞追踪和突触分析，与我们在“经典”免疫学测定方面的专业知识相结合，研究这种“集体”激活；占据同一反应性淋巴结的多个 T 细胞的激活。发现那是其他人证实，存在一个“关键分化期”，与个体激活 T 细胞克隆组合在一起形成 T-T 突触介导的接触相一致。根据我们和该领域其他人的工作，我们发现两者都是自然的。以及细胞-细胞相互作用的合成形式，这些相互作用可以在引发 CD8 反应期间利用，并且这些将改变病毒攻击的结果。通过解决这一假设，我们的目标是最终提供关于免疫细胞如何发挥作用的基本原理理解。共同激活和改善 CD8 反应的疫苗接种。