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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：
10758027
负责人：
Beth Ann Tamburini
金额：
$ 7.25万
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 2026-03-31
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10758027
关键词：
Address Affect Antigen Presentation Antigens Archives Attenuated Vaccines Award Bar Codes CD8-Positive T-Lymphocytes Caveolins Cell Communication Cell Shape Cell physiology Cells Cellular Immunity Communication Conjugate Vaccines DNA Data Dendritic Cells Development Event Exocytosis Flow Cytometry Funding Future Gene Expression Profile Genes Genetic Transcription Hand Hematopoietic ICAM1 gene Immune response Immunity Immunologic Memory Infection Inflammation Inflammatory Lead Learning Lymphatic Lymphatic Endothelial Cells Measures Memory Messenger RNA Methodology Methods Molecular Process Proliferating Proteins Publishing Secondary to Signal Transduction Source Surface T cell response T memory cell Techniques Technology Time Tissues Vaccination Vaccine Design Vaccines Viral Viral Antigens Virus Virus Diseases adaptive immune response antigen detection cell type design emerging pathogen genomic platform grasp improved lymph nodes novel prevent programs protein degradation secondary infection single cell mRNA sequencing subcutaneous trafficking transcriptome vaccination strategy vaccine strategy

项目摘要

Project summary: We and others have demonstrated that antigens derived from infectious viral infections persist in the host for extended periods of time, well beyond the time in which the infection is cleared from the host. Our lab has specifically identified that antigens derived from both vaccination and viral infections persist or are archived by the host lymphatic endothelial cells (LEC)s, identifying the source of archived antigens. We have published that this archived antigen maintains a more effector like pool of antigen specific memory cells which enhances the clearance of a secondary infectious challenge. Identification of key mechanisms involved in antigen archiving during vaccination is critical for our understanding of enhanced protective immunity to vaccination. While we have established many important criteria for antigen archiving and protective immunity, in this renewal application we aim to dive deeper into the cell types involved and the processes required. We aim to better appreciate how the expression of subset specific genes, now discovered in both lymphatic endothelial cells and dendritic cells, may be required for antigen handling, the implications of which could affect antigen archiving and protective immunity. We have established a novel methodology leveraging the 10x genomics platform to identify DNA-antigen conjugates for the study of antigen dispersal over long periods of time. With this methodology and technology in hand we now have the capability to accurately and faithfully measure cell types that acquire antigens as well as the exact number of antigens within each cell over time. Using these studies we have identified several novel findings based on antigen amount and transcriptional signature to lead us to the hypothesis that specific LECs and DCs, based on their transcriptional program, contribute to the acquisition, retention and exchange of antigens. Furthermore, this handling of antigens by LECs and DCs can be manipulated by other inflammatory events that cause antigen release and presentation, and as a result, improve immune responses to secondary and heterologous infections.

项目总结: