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）：免疫系统的适应性分支由 B 淋巴细胞和 T 淋巴细胞组成。 CD8 T 细胞是介导细胞内病原体和肿瘤免疫的关键角色。在 MHC I 类环境中遇到抗原的 CD8 T 细胞被激活并启动增殖和分化为效应细胞毒性 T 淋巴细胞 (CTL) 的程序。通常，为了应对急性病毒感染，初始 CD8 T 细胞可能在 6 天内经历超过 15 次分裂，产生数千个效应子代。在这种反应的高峰期（也称为初次反应），抗原通常已被清除，在接下来的几天内，超过 90% 的效应 CD8 T 细胞死亡。这个称为收缩的过程留下了一小部分幸存的 T 细胞，它们作为长寿命的记忆细胞持续存在。除了它们的寿命之外，记忆细胞的另一个特征是它们能够以增强的功效来响应相同抗原的再攻击（​​二次响应）。这些特征加上数量的增加，使记忆 CD8+ T 细胞能够针对以前遇到的病原体提供有效、持久的免疫力。虽然许多已建立的疫苗接种计划主要依赖于有效的抗体反应，但当前的挑战，例如疟疾、艾滋病毒和结核病，似乎需要采取不同的方法。 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）侵害的关键角色。彻底了解 CD8 T 细胞记忆如何产生和维持将为我们提供更多见解和更好的疫苗接种策略。我们希望将研究重点放在 CD8 T 细胞反应中人们知之甚少的收缩部分。我研究的主要目标是了解 CD8 T 细胞从效应阶段到记忆阶段的转变是如何受到调节的。未来 3 年更具体的目标是阐明控制 CD8 T 细胞反应的收缩期和随后的记忆期某些方面的机制。 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进疫苗接种策略。