Cooperation between lymphatic stroma and hematopoietic cells shapes protective immunity

淋巴基质和造血细胞之间的合作形成保护性免疫

基本信息

批准号：
9225166
负责人：
Beth Ann Tamburini
金额：
$ 38.54万
依托单位：
UNIVERSITY OF COLORADO DENVER
依托单位国家：
美国
项目类别：
财政年份：
2016
资助国家：
美国
起止时间：
2016-02-16 至 2021-01-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9225166
关键词：
Address Affect Alpha Cell Antigen Presentation Antigen-Presenting Cells Antigens Apoptosis Apoptotic Archives Autoantigens Cell Proliferation Cell Shape Cell division Cell physiology Cells Complement Contracts Data Dendritic Cells Documentation Effector Cell Gatekeeping Goals Hand Hematopoietic Homeostasis Immune response Immunity Immunization Immunologic Memory Infection Inflammatory Inflammatory Response Lead Libraries Lymphatic Lymphatic Endothelial Cells Lymphatic vessel Mediating Memory Mind Modeling Population Predisposition Prevention Process Publications Receptor Cell Recruitment Activity Resolution Retrieval Role Self Tolerance Shapes Speed Stimulus Stromal Cells T memory cell T-Lymphocyte Testing Time Vaccination Vaccines Viral Virus Diseases Work cell type chemokine exosome lymph nodes novel public health relevance rate of change receptor response uptake

项目摘要

DESCRIPTION (provided by applicant): Our preliminary data suggests that antigen uptake is dependent on the expansion of LECs. If expansion of the lymph node leads to antigen archiving, does contraction of the lymph node lead to antigen hand-off? There appear to be two mechanisms of antigen hand-off/exchange from LECs to hematopoietically derived APCs. First, contraction of the lymph node results in LEC apoptosis as the lymph node decreases in size. Presumably some of the LECs that apoptose are holding onto antigen. Thus, archived antigen is given to dendritic cells or other antigen presenting cells through the uptake of apoptotic LECs. A second mechanism of antigen exchange occurs after the lymph node has returned to normal size. We will address mechanisms of steady state antigen exchange for which we have preliminary data. We will first evaluate if antigen exchange in the steady state is complement mediated and second evaluate if antigen exchange in the steady state is exosome mediated. Our last aim will test how multiple rounds of expansion and contraction affects antigen archiving and antigen exchange. The extent with which antigen is archived, i.e. which LECs archive antigen, how it is retained during lymph node expansion and contraction, and how it is retained and acquired after multiple rounds of infection is the focus of this aim. Our overarching hypothesis is that expansion and contraction of the lymph node changes the library of antigens that LECs acquire during infections or immunizations by exchanging antigen with hematopoietically derived APCs. The resulting changes in antigen retention on LECs as a result of antigen exchange likely leads to differences in susceptibility to re-infection and prolonged immunity.

描述（由申请人提供）：我们的初步数据表明，抗原的摄取取决于 LEC 的扩张，如果淋巴结的扩张导致抗原归档，那么淋巴结的收缩是否会导致抗原传递？从 LEC 到造血来源的 APC 的抗原传递/交换的两种机制首先，随着淋巴结尺寸的减小，淋巴结收缩导致 LEC 凋亡。因此，通过摄取凋亡的 LEC 将存档的抗原提供给树突状细胞或其他抗原呈递细胞，在淋巴结恢复到正常大小后发生第二种抗原交换机制。我们将首先评估稳定状态下的抗原交换是否是补体介导的，然后评估稳定状态下的抗原交换是否是外泌体介导的。影响抗原存档和抗原交换。抗原存档的程度，即哪些LEC存档抗原，在淋巴结扩张和收缩过程中如何保留抗原，以及在多轮感染后如何保留和获取抗原，是我们的重点。总体假设是，淋巴结的扩张和收缩通过与造血来源的 APC 交换抗原，改变了 LEC 在感染或免疫过程中获得的抗原库，从而导致 LEC 上的抗原保留发生变化。抗原交换的进行可能会导致对再次感染的易感性差异和延长免疫力。