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

• 批准号: 9122818
• 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
• 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/9122818
• 关键词: Address; Affect; 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; Goals; Hand; Hematopoietic; Homeostasis; Immune; Immune response; Immunity; Immunization; 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

 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（由适用提供）：我们的初步数据表明抗原摄取取决于LEC的扩展。如果淋巴结的膨胀导致抗原归档，淋巴结的收缩会导致抗原交接吗？从LEC到造血衍生的APC，似乎有两种抗原交接/交换的机制。首先，随着淋巴结的大小下降，淋巴结的收缩会导致LEC凋亡。大概有些凋亡固定在抗原上的LEC。这是通过吸收凋亡的LEC的归档抗原对树突状细胞或其他抗原呈递细胞的。淋巴结恢复正常后，发生抗原交换的第二种机制。我们将解决我们拥有初步数据的稳态抗原交换的机制。我们将首先评估是否完全介导了稳定状态的抗原交换，并且第二次评估是否是稳态中的抗原交换。我们的最后一个目标将测试多轮扩张和合同如何影响抗原归档和抗原交换。对抗原存档的程度，即哪些LEC储存抗原，在淋巴结扩张和收缩期间如何保留抗原，以及在多轮感染后如何将其保留和获取。我们的总体假设是，淋巴结的膨胀和收缩改变了LEC在感染期间获得的抗原文库或通过与造血衍生的APC交换抗原在感染期间获得的抗原图书馆。由于抗原交换而导致的LEC抗原保留的变化可能会导致重新感染和延长免疫抑制的易感性差异。