CD8 T cell Immunity to Influenza

这个项目的目标是获得关于CD8 T细胞在保护 预防流感感染。CD8 T细胞反应被认为在清除 感染和通过动物模型研究建立保护性免疫。然而， 甲型流感病毒特异性CD8 T细胞免疫应答的定量和定性特征 自然感染和疫苗在人类宿主中还没有得到系统的调查。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CD8 T细胞免疫功能的研究 甲型流感抗原。将在所有接种疫苗的年龄段队列中进行前瞻性评估 灭活或活的减毒流感疫苗以及自然感染甲型流感的儿童。这个 具体目标是：1.表征甲型流感前后特异性CD8 T细胞反应 幼童接种灭活流感疫苗或减毒活流感疫苗 成年人和老年人。我们假设免疫将诱导效应性和记忆性CD8T细胞 不同时间点的反应，表现为多种表型和T的特定模式 细胞功能。我们预计疫苗类型和年龄的不同会有不同的反应。2.为了描述数字， 甲型流感病毒特异性效应T细胞和记忆性CD8 T细胞的表型和功能 急性流感。评估儿童的抗病毒CD8 T细胞反应可以研究主要的CD8 受试者暴露于NATve后的T细胞反应。我们假设CD8 T细胞反应是由 自然感染将类似于对活疫苗的反应。该项目是我们协调的 努力解决T细胞和B细胞反应以及自然杀伤细胞对甲型流感的反应 并将提供有关CD8 T细胞免疫的新信息 宿主对甲型流感的总体反应情况。这一信息对于提供 在潜在的甲型流感大流行期间，在自然发生或 生物恐怖事件。

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.