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CD8 T cell Immunity to Influenza

CD8 T 细胞对流感的免疫

基本信息

批准号：
7657178
负责人：
Ann Arvin
金额：
$ 16.19万
依托单位：
STANFORD UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2008
资助国家：
美国
起止时间：
2008-04-01 至 2009-03-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7657178
关键词：
Acute Address Adhesions Adult Age Animal Model Antigens Antiviral Agents Attenuated Attenuated Live Virus Vaccine Attenuated Vaccines B-Lymphocytes Blood specimen CD28 gene CD4 Positive T Lymphocytes CD8B1 gene Cell physiology Characteristics Child Clinical Research Color Data Set Detection Elderly Evaluation Event Exposure to Flow Cytometry Frequencies Human Immune Immune response Immunity Immunization Immunology Individual Infection Influenza Influenza A virus Investigation Knowledge Life Medical Surveillance Memory Methods NCAM1 gene Nose Numbers Pattern Phenotype Play Polymerase Chain Reaction Population Predisposition Production Research Project Grants Risk Role Seasons T memory cell T-Lymphocyte Techniques Testing Thinking Time Translational Research Vaccination Vaccines Virus Virus Diseases Week age group base biodefense chemokine receptor cohort human subject influenza virus vaccine pandemic disease pathogen peripheral blood prospective research study response tool young adult

项目摘要

The objective of this project is to acquire new knowledge about the role of the CD8 T cells in protecting against influenza infection. The CD8 T cell response is thought to play a pivotal role in clearing infection and establishing protective immunity from studies in animal models. However, the quantitative and qualitative characteristics of the influenza A virus-specific CD8 T cell response to natural infection and vaccines have not been investigated systematically in the human host. We propose to evaluate influenza A virus-specific CD8 T cells in child populations and adults. Experiments will use multi-color flow cytometry-based techniques which overcome technical obstacles to assessing CD8 T cell immunity in human populations, including children, to characterize CD8 T cells specific for influenza A antigens. Prospective evaluations will be done in all age cohorts who are immunized with inactivated or live attenuated influenza vaccines and in children with natural influenza A infection. The Specific Aims are: 1. To characterize the influenza A-specific CD8 T cell response before and after administration of inactivated influenza vaccine or live attenuated influenza vaccine to children, young adults, and older adults. We hypothesize that immunization will induce effector and memory CD8 T cell responses at different time points, as characterized by specific patterns of multiple phenotypes and T cell functions. We expect responses to differ by vaccine type, and age. 2. To characterize the number, phenotype and functions of influenza A virus-specific effector and memory CD8 T cells in children with acute influenza. To evaluate antiviral CD8 T cell responses in children allows study of the primary CD8 T cell response in naTve exposed, subjects. We hypothesize that CD8 T cell responses induced by natural infection will resemble responses to live vaccine. This project is a component of our coordinated efforts addressing T cell and B cell responses as well as natural killer responses to influenza A using the same cohort of human subjects and will provide new information on the CD8 T cell immunity in the context of the overall host responses to influenza A. This information will be critical for providing enhanced protection during a potential influenza A pandemic while it is naturally occurring or a bioterrorist event.

该项目的目标是获得有关 CD8 T 细胞在保护中的作用的新知识对抗流感感染。 CD8 T 细胞反应被认为在清除过程中发挥关键作用感染并通过动物模型研究建立保护性免疫力。然而，甲型流感病毒特异性 CD8 T 细胞反应的定量和定性特征尚未在人类宿主中系统地研究自然感染和疫苗。我们建议评估儿童和成人中甲型流感病毒特异性 CD8 T 细胞。实验将使用基于多色流式细胞术的技术，克服评估的技术障碍包括儿童在内的人群中的 CD8 T 细胞免疫，以表征 CD8 T 细胞特异性甲型流感抗原。将对所有接种疫苗的年龄组进行前瞻性评估灭活或减毒活流感疫苗以及自然感染甲型流感的儿童。这具体目标是： 1. 表征甲型流感特异性 CD8 T 细胞反应前后的特征给儿童、青少年接种灭活流感疫苗或减毒活流感疫苗成年人和老年人。我们假设免疫会诱导效应和记忆 CD8 T 细胞不同时间点的反应，以多种表型和 T 的特定模式为特征细胞功能。我们预计反应会因疫苗类型和年龄而异。 2. 表征数字，儿童甲型流感病毒特异性效应细胞和记忆CD8 T细胞的表型和功能急性流感。评估儿童抗病毒 CD8 T 细胞反应可以研究初级 CD8 初次暴露的受试者中的 T 细胞反应。我们假设 CD8 T 细胞反应由自然感染将类似于对活疫苗的反应。该项目是我们协调的一个组成部分努力解决 T 细胞和 B 细胞反应以及对甲型流感的自然杀伤反应，使用同一组人类受试者将提供有关 CD8 T 细胞免疫的新信息宿主对甲型流感的总体反应的背景。该信息对于提供在甲型流感自然发生或发生潜在甲型流感大流行期间加强保护生物恐怖事件。