CD8 Tau cell contraction and memory formation

CD8 Tau细胞收缩和记忆形成

• 批准号: 7660600
• 负责人: Martin Prlic
• 金额: $ 9万
• 依托单位: UNIVERSITY OF WASHINGTON
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-08-01 至 2010-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7660600
• 关键词: Acute; Address; Affinity; Antibody Formation; Antigens; Autophagocytosis; Bacteria; Biological Models; CD8B1 gene; Caspase; Cell Death; Cell Survival; Cells; Cues; Cytotoxic T-Lymphocytes; Data; Effector Cell; Genes; Goals; HIV; Immune system; Immunity; Infection; Inflammation; Inflammatory; Lead; Left; Life; Light; Longevity; MHC Class I Genes; Malaria; Mediating; Memory; Molecular; Phase; Process; Research; Research Personnel; Role; Staging; Stimulus; T memory cell; T-Lymphocyte; Testing; Time; Tuberculosis; Vaccination; Vaccines; Virus; Virus Diseases; improved; insight; overexpression; pathogen; programs; research study; response; tau Proteins; transcription factor; tumor; vaccination strategy

DESCRIPTION (provided by applicant): The adaptive branch of the immune system consists of B and T lymphocytes. CD8 T cells are key players in mediating immunity to intracellular pathogens and tumors. CD8 T cells that encounter antigen in the context of MHC class I become activated and initiate a program of proliferation and differentiation into effector cytotoxic T lymphocytes (CTL). Typically, in response to an acute viral infection, a naive CD8 T cell may go through more than 15 divisions in 6 days to generate thousands of effector progeny. At the peak of this response, also called the primary response, antigen has typically been cleared and in the following days more than 90% of the effector CD8 T cells die. This process called contraction leaves behind a surviving fraction of T cells that persists as long-lived memory cells. Apart from their longevity, memory cells are further characterized by their ability to respond with enhanced efficacy to rechallenge with the same antigen (secondary response). These features, plus their increased numbers, allow memory CD8+ T cell to provide efficient long lasting immunity against previously encountered pathogens. While many established vaccination programs are mainly dependent on an efficient antibody response, current challenges such as malaria, HIV and tuberculosis appear to require a different approach. CD8 T cells are a key player protecting us against intracellular pathogens (such as viruses or certain intracellular bacteria). A thorough understanding of how CD8 T cell memory is generated and maintained will provide us with more insight and better vaccination strategies. We want to focus our research on the poorly understood contraction part of the CD8 T cell response. The broad goal of my research is to understand how the transition of CD8 T cells from the effector to the memory stage is regulated. The more specific goal for the next 3 years is to shed light on the mechanisms that control certain aspects of the contraction phase and the ensuing memory phase of the CD8 T cell response. RELEVANCE: The proposed research will help us understand better how the immune system responds to infection. This will aid in developing and improving vaccination strategies.

描述（由申请人提供）：免疫系统的自适应分支由B和T淋巴细胞组成。 CD8 T细胞是介导对细胞内病原体和肿瘤免疫力的关键参与者。在MHC I类中遇到抗原的CD8 T细胞被激活，并引发了增殖和分化为效应细胞毒性T淋巴细胞（CTL）的程序。通常，对于急性病毒感染的响应，幼稚的CD8 T细胞可能会在6天内经过15个以上的划分，以产生数千个效应子后代。在此反应的峰值上，也称为主要反应，通常已经清除了抗原，在接下来的几天中，效应子CD8 T细胞的90％以上死亡。这个称为收缩的过程留下了持续存在的T细胞的持续时间，这些细胞持续了长期记忆细胞。除了寿命外，记忆细胞还进一步的特征是它们具有增强功效以使用相同的抗原恢复目标的能力（次要反应）。这些功能以及增加的数字，使记忆CD8+ T细胞可针对先前遇到的病原体提供有效的持久免疫力。尽管许多已建立的疫苗接种计划主要取决于有效的抗体反应，但诸如疟疾，HIV和结核病等当前挑战似乎需要不同的方法。 CD8 T细胞是保护我们免受细胞内病原体（例如病毒或某些细胞内细菌）的关键参与者。对CD8 T细胞记忆的产生和维护的透彻了解将为我们提供更多的见识和更好的疫苗接种策略。我们希望将研究重点放在CD8 T细胞反应的不理解的收缩部分上。我的研究的广泛目标是了解如何调节CD8 T细胞从效应子到记忆阶段的过渡。接下来的3年的更具体的目标是阐明控制收缩阶段某些方面的机制以及CD8 T细胞响应的随之而来的记忆阶段。 相关性：拟议的研究将帮助我们更好地了解免疫系统如何应对感染。这将有助于制定和改善疫苗接种策略。