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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(申请人提供)：我们的初步数据表明，抗原摄取依赖于晶状体上皮细胞的扩张。如果淋巴结扩张导致抗原聚集，那么淋巴结收缩是否会导致抗原转移？从LECs到造血源性APC的抗原传递/交换似乎有两种机制。首先，随着淋巴结的缩小，淋巴结的收缩会导致LEC的凋亡。据推测，一些凋亡性的晶状体上皮细胞正在紧握抗原。因此，存档的抗原通过摄取凋亡的LECs给予树突状细胞或其他抗原提呈细胞。第二种抗原交换机制发生在淋巴结恢复到正常大小之后。我们将讨论我们已有初步数据的稳态抗原交换机制。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，其次评估稳定状态下的抗原交换是否由外切体介导。我们的最后一个目标是测试多轮扩张和收缩如何影响抗原存档和抗原交换。抗原被存档的程度，即哪些LECs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得抗原，是这一目标的重点。我们的主要假设是，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LECs在感染或免疫期间获得的抗原库。由于抗原交换导致晶状体上皮细胞上抗原滞留的变化，可能导致对再次感染和延长免疫的不同易感性。