CD8 Tau cell contraction and memory formation

描述（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细胞在介导对细胞内病原体和肿瘤的免疫中起着关键作用。CD8 T细胞在MHC I类环境中遇到抗原后被激活，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，在对急性病毒感染的反应中，初始CD8 T细胞可能在6天内经历15次以上的分裂，以产生数千个效应子代。在这种反应的高峰期，也被称为初级反应，抗原通常被清除，在接下来的几天里，超过90%的效应CD8 T细胞死亡。这个被称为收缩的过程留下了一部分存活的T细胞，这些T细胞作为长期存在的记忆细胞存在。除了它们的寿命外，记忆细胞的另一个特点是它们对相同抗原的再挑战有更强的反应能力（二次反应）。这些特征，加上它们数量的增加，使记忆性CD8+ T细胞能够对以前遇到的病原体提供有效的长期免疫。虽然许多已建立的疫苗接种规划主要依赖于有效的抗体反应，但目前的挑战，如疟疾、艾滋病毒和结核病，似乎需要一种不同的方法。CD8 T细胞是保护我们免受细胞内病原体（如病毒或某些细胞内细菌）侵害的关键角色。彻底了解CD8 T细胞记忆是如何产生和维持的，将为我们提供更多的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细胞反应中鲜为人知的收缩部分。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被调节的。未来3年更具体的目标是阐明控制CD8 T细胞收缩期和随后的记忆期某些方面的机制。

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.