CD8 Tau cell contraction and memory formation

CD8 Tau细胞收缩和记忆形成

基本信息

批准号：
8282722
负责人：
Martin Prlic
金额：
$ 24.59万
依托单位：
FRED HUTCHINSON CANCER RESEARCH CENTER
依托单位国家：
美国
项目类别：
财政年份：
2009
资助国家：
美国
起止时间：
2009-08-01 至 2013-09-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8282722
关键词：
Acute Address Affect Affinity Agreement Antibody Formation Antigens Applications Grants Autophagocytosis Award B-Lymphocytes Bacteria Biological Models Blood specimen CD8B1 gene Caspase Cell Count Cell Death Cell Survival Cells Control Groups Cues Cytotoxic T-Lymphocytes Data Dendritic Cells Distal Effector Cell Epitopes Frequencies Genes Goals Grant Granzyme HIV Hour Immune system Immunity In Vitro Infection Inflammation Inflammatory Knockout Mice Lead Life Light Listeria monocytogenes Longevity MHC Class I Genes Malaria Manuscripts Mature T-Lymphocyte Mediating Memory Molecular Mouse Strains Mus OVA-8 Ovalbumin Ovary Pathway interactions Phase Phenotype Physiologic pulse Population Process Progress Reports Proliferating Property Publications Published Comment Publishing Reading Recombinants Regimen Reporter Research Research Proposals Role Series Signal Pathway Spottings Staging Staining method Stains Stem cells Stimulus T cell response T memory cell T-Cell Activation T-Cell Development T-Lymphocyte Testing Thymus Gland Time Transgenic Mice Tuberculosis Update Vaccination Vaccines Vaccinia Vaccinium Vesicular stomatitis Indiana virus Virus Virus Diseases Work base beta catenin fitness follow-up imprint improved in vivo insight knock-down memory recall overexpression pathogen programs promoter research study response tau Proteins transcription factor transgene expression tumor vaccination strategy

项目摘要

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. CDS 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 CDS 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 CDS 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, cun^ent challenges such as malaria, HIV and tuberculosis appear to require a different approach. CDS T cells are a key player protecting us against intracellular pathogens (such as viruses or certain intracellular bacteria). A thorough understanding of how CDS 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 CDS T cell response. The broad goal of my research is to understand how the transition of CDS T cells from the effector to the memory stage is regulated and how a fit memory T cell pool is generated. The more specific goal for the next two years is to shed light on the mechanisms that control certain aspects of the contraction phase and the ensuing memory phase of the CDS T cell response.

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 细胞是关键介导细胞内病原体和肿瘤免疫的参与者。 CDS T 细胞遇到抗原 MHC I 类环境被激活并启动增殖和分化程序效应细胞毒性T淋巴细胞（CTL）。通常，为了应对急性病毒感染，幼稚 CDS T 细胞可能在 6 天内经历超过 15 个分裂，产生数千个效应子代。在巅峰时期这种反应，也称为初级反应，抗原通常已被清除，并在接下来的几天内超过 90% 的效应 CDS T 细胞死亡。这个称为收缩的过程留下了幸存的作为长寿命记忆细胞持续存在的 T 细胞的一部分。记忆细胞除了寿命长之外，进一步的特点是它们能够以增强的功效响应相同抗原的再次攻击（二次响应）。这些特征，加上数量的增加，使得记忆 CD8+ T 细胞能够提供针对以前遇到的病原体的有效持久的免疫力。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，当前的挑战，如疟疾、艾滋病毒和结核病，似乎需要采取不同的方法。 CDS 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病原体）侵害的关键角色。细菌）。彻底了解 CDS T 细胞记忆如何生成和维持将为我们提供帮助拥有更多的洞察力和更好的疫苗接种策略。我们希望将研究重点放在 CDS 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 CDS T 细胞如何从效应细胞转变为效应细胞记忆阶段的调节以及如何生成合适的记忆 T 细胞库。更具体的目标是未来两年将阐明控制收缩阶段某些方面的机制 CDS T 细胞反应的随后记忆阶段。