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.

免疫系统的自适应分支由B和T淋巴细胞组成。 CD8 T细胞是关键介导对细胞内病原体和肿瘤的免疫力的参与者。遇到抗原的CD T细胞 MHC类的背景I被激活，并启动一个扩散和分化的程序效应细胞毒性T淋巴细胞（CTL）。通常，为了响应急性病毒感染，幼稚的CD T细胞在6天内可能会经历15个以上的分区，以产生数千个效应子后代。在这种反应，也称为主要响应，通常已清除抗原，并在接下来的几天内超过90％的效应子CD T细胞死亡。这个称为收缩的过程留下了幸存的 T细胞的一部分是长期寿命的记忆细胞。除了它们的寿命外，记忆细胞是进一步的特征是它们具有增强功效的响应能力，可以使用相同的抗原进行弥补（次要响应）。这些功能以及增加的数字，允许内存CD8+ T单元提供有效的持久免疫力针对先前遇到的病原体。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，艾滋病毒和结核病等挑战似乎需要不同的方法。 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）的关键参与者细菌）。对CDS T细胞内存的生成和维护的透彻了解将为我们提供采用更多洞察力和更好的疫苗接种策略。我们希望将研究集中在CDS T细胞反应的收缩部分上。我的研究的广泛目标是了解CDS T细胞从效应子到效应器的过渡如何记忆阶段受到调节，以及如何生成拟合存储器T单元池。更具体的目标接下来的两年是阐明控制收缩阶段某些方面和 CDS T细胞响应的随之而来的记忆阶段。