NONHUMAN PRIMATE MODEL OF IMMUNOSENESCENCE AND VACCINATION

非人灵长类动物免疫衰老模型和疫苗接种

基本信息

批准号：
8358107
负责人：
Elizabeth Schmidt Didier
金额：
$ 3.72万
依托单位：
TULANE UNIVERSITY OF LOUISIANA
依托单位国家：
美国
项目类别：
财政年份：
2011
资助国家：
美国
起止时间：
2011-05-01 至 2012-04-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8358107
关键词：
20 year old Age Aging Animals B-Lymphocytes Basophils Blood Cells Blood Platelets Bromodeoxyuridine CCL2 gene CD4 Positive T Lymphocytes CD8B1 gene Data Analyses Dendritic Cells Elderly Erythrocytes Flow Cytometry Funding Grant Human Immune Immune response Immune system Immunology Interleukin-18 Interleukin-2 Interleukin-5 Label Linear Regressions Lymphocyte Macaca mulatta Measures Methods Modeling National Center for Research Resources Natural Killer Cells Peripheral Plasma Population Primates Principal Investigator Research Research Infrastructure Resources Source T memory cell T-Lymphocyte TNF gene Testing United States National Institutes of Health Vaccination Vascular Endothelial Growth Factors base cost cytokine eosinophil immunosenescence improved monocyte neutrophil nonhuman primate public health priorities vaccine efficacy

项目摘要

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. The elderly population is growing in number and proportion to the total population. During aging, the immune system begins to falter, so methods to improve immune responses and vaccine efficacy in the elderly is a public health priority. Non-human primates are phylogenetically related and physiologically similar to humans and provide a useful model to study immunology of aging. The purpose of this study was to define changes in the peripheral immune system in rhesus macaques of varying ages. Flow cytometry of blood cells and multiplex cytokine levels in plasma were evaluated in 35 rhesus macaques ranging in age from 3.2 - 20 years. Linear regression was used to analyze the data for statistically significant changes (i.e. P 0.05) associated with age. Results indicated that with increasing age, significant declines were observed in numbers of neutrophils, eosinophils, basophils, and lymphocytes. No statistically significant changes in total numbers of monocytes, dendritic cells (DC), erythrocytes, or platelets were noted. Within the lymphocyte population, significant decreases in B lymphocytes were detected while numbers of total NK cells and T cells did not significantly change with increasing age. Examination within the T cell population, however, indicated significant declines in the number of naive CD4+ T cells and naive CD8+ T cells, as well as gd+ T cells with increasing age, whereas the number of CD8+ effector-memory T cells increased with age. Although the number of DCs did not significantly change with advancing age, the turnover rate of pDCs, as measured by BrdU-labeling and flow cytometry, was significantly higher in the 18-20 year-old group of animals compared to younger groups of animals. Among the cytokines tested in plasma using the Milliplex MAP non-human primate cytokine panel (23-mer) kit, TNF-a, IL-2, MCP-1, sCD40L, TGF-a, VEGF, and IL-18 levels significantly increased with increasing age of the animals whereas IL-5 was the only cytokine tested that decreased with increasing age. These early results provide a basis to further characterize immunosenescence in a non-human primate model, and for developing strategies to improve immune status and vaccine efficacy in the elderly.

该副本是利用资源的众多研究子项目之一由NIH/NCRR资助的中心赠款提供。对该子弹的主要支持而且，副投影的主要研究员可能是其他来源提供的包括其他NIH来源。列出的总费用可能代表subproject使用的中心基础架构的估计量， NCRR赠款不直接向子弹或副本人员提供的直接资金。老年人口的数量增长，与总人口成比例。在衰老期间，免疫系统开始流动，因此改善老年人的免疫反应和疫苗功效的方法是公共卫生的优先事项。非人类灵长类动物在系统发育相关和生理上与人类相似，并为研究衰老的免疫学提供了有用的模型。这项研究的目的是定义不同年龄段的恒河猕猴外周种免疫系统的变化。在35个恒河猕猴中评估了血浆中血细胞和多重细胞因子水平的流式细胞仪，年龄为3.2-20岁。线性回归用于分析与年龄相关的统计学上显着变化（即p 0.05）的数据。结果表明，随着年龄的增长，中性粒细胞，嗜酸性粒细胞，嗜碱性粒细胞和淋巴细胞的数量显着下降。没有发现单核细胞，树突状细胞（DC），红细胞或血小板的统计显着变化。在淋巴细胞种群中，检测到B淋巴细胞的显着降低，而总NK细胞和T细胞的数量随着年龄的增长而没有显着变化。然而，在T细胞种群中的检查表明，幼稚的CD4+ T细胞和幼稚的CD8+ T细胞的数量以及年龄增加的GD+ T细胞的数量显着下降，而CD8+效应 - 内存T细胞的数量随着年龄的增长而增加。尽管随着年龄的增长，DC的数量并未显着变化，但与年轻动物相比，通过BRDU标记和流式细胞仪测量的PDC的周转率显着更高。在血浆中使用的细胞因子中，使用Milliplex MAP非人类灵长类动物细胞因子面板（23-mer）试剂盒，TNF-A，IL-2，MCP-1，SCD40L，TGF-A，TGF-A，VEGF，VEGF和IL-18水平显着增加，随着动物IL-5年龄的增长，随着年龄的增长而增加了CyTokine测试，以增加cytokine的测试。这些早期结果为进一步表征非人类灵长类动物模型的免疫衰老提供了基础，并制定了提高老年人免疫状态和疫苗功效的策略。