Quantitative models of CD8+ T-cell memory

CD8 T 细胞记忆的定量模型

• 批准号: 7558509
• 负责人: RUSTOM NOSHIR ANTIA
• 金额: $ 18.76万
• 依托单位: EMORY UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2001
• 资助国家: 美国
• 起止时间: 2001-07-01 至 2012-02-29
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7558509
• 关键词: Acute; Age; Area; CD8-Positive T-Lymphocytes; CD8B1 gene; Cell Aging; Cell Count; Cell model; Cells; Cessation of life; Childhood; Data; Death Rate; Development; Diamond; Epitopes; Exposure to; Goals; Grant; Human; Immune; Immune response; Immunologic Memory; Inbred BALB C Mice; Infection; Label; Longevity; Lymphocytic choriomeningitis virus; Measurement; Memory; Memory Loss; Modeling; Mus; Population; Population Heterogeneity; Process; Property; Protocols documentation; Research Personnel; Short-Term Memory; T memory cell; Testing; Time; Vaccination; Vaccines; Vertebrates; Virus; Work; aging population; design; mathematical model; pathogen; programs; research study; telomere; tool

DESCRIPTION (provided by applicant): While immune memory is a central feature of the immune response of vertebrates, many fundamental questions remain largely unanswered. For example we don't really know how long memory cell populations for a given pathogen will be maintained in the absence of restimulation with that pathogen, or how the decline of memory depends on exposure to new pathogens. We would like quantitative answers to these questions, and this requires the development of mathematical models. Models need to be brought into contact with experiments. To do this one needs to develop tools to analyze experimental data (such as CFSE data) in ways which allow the models to be validated. Our long-term goal is to establish a quantitative picture of how immune memory works. Such a picture is important for the design of vaccination protocols in various situations, such as in an aging population. Specific Aim 1: We will develop tools to quantitatively describe division and death of a heterogeneous population of cells from CFSE measurements (which tells us the number of cells as well as the number of divisions they have undergone). Specific Aim 2: We will develop and validate models for the longevity of CD8+ T cell memory. There are three components to this specific aim. 1. We will experimentally validate our current model (formulated in our previous grant). 2. The model developed so far works over the time scale of a few years. We will extend the model to generate a more complete description of immunological memory over the lifespan of humans. We will do this by developing models which consider cross-reactive stimulation and replicative senescence. 3. We will consider the implications of our models for vaccination by considering the loss of memory in an ageing population, the optimal boosting strategy as well as the order of delivery of multiple childhood vaccines.

描述（由申请人提供）：虽然免疫记忆是脊椎动物免疫反应的核心特征，但许多基本问题基本上仍未得到解决。例如，我们真的不知道在没有该病原体的情况下，在没有再刺激的情况下，将保持多长时间的记忆细胞群体，或者记忆的下降如何取决于暴露于新病原体。我们希望对这些问题进行定量答案，这需要开发数学模型。模型需要与实验接触。为此，需要开发工具来以允许验证模型的方式分析实验数据（例如CFSE数据）。我们的长期目标是确定免疫记忆如何工作的定量图。这样的图片对于在各种情况下（例如人口老龄化）的疫苗接种方案的设计很重要。具体目的1：我们将开发工具，以定量描述CFSE测量值的异质细胞种群的分裂和死亡（这告诉我们细胞的数量以及它们经历的分裂数量）。特定目标2：我们将开发和验证CD8+ T细胞存储器寿命的模型。这个特定目标有三个组成部分。 1。我们将通过实验验证当前的模型（在以前的赠款中配制）。 2。到目前为止，该模型在几年的时间范围内工作。我们将扩展该模型，以在人类的寿命中生成更完整的免疫记忆描述。我们将通过开发考虑交叉反应刺激和复制衰老的模型来做到这一点。 3。我们将通过考虑年龄衰老的记忆力损失，最佳的增强策略以及多种儿童疫苗的交付顺序来考虑模型对疫苗接种的影响。