The T cell ecosystem: How do T cells co-exist and co-regulate each other during an immune response?

T 细胞生态系统：在免疫反应过程中，T 细胞如何共存并相互调节？

• 批准号: BB/R015651/1
• 负责人: Audrey Gerard
• 金额: $ 65.54万
• 依托单位: University of Oxford
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2018
• 资助国家: 英国
• 起止时间: 2018 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=BB%2FR015651%2F1
• 关键词: cell; ecosystem; How; do; cells

Most entities, such as humans, animals or plants, are living in and benefit from being in a group, society or ecosystem. For example, bees inform each other when they find a food source, and keep all the food they individually find into the beehive, which benefits the whole colony. This proposal is based on the hypothesis some white blood cells called CD8 T cells also organise themselves as an ecosystem during healthy responses, and that this is beneficial for the overall outcome. Each CD8 T cell clone is unique, as it expresses a specific T cell receptor that recognises different sets of antigens with different affinities. It has been proposed that this diversity was required for long-term immunity towards viruses. Diversity happens despite the fact that some CD8 T cells have a competitive advantage and are sufficient to control infections, suggesting that the breadth of CD8 T cell clones recruited to a response is actively regulated. How different T cell clones co-exist and communicate to achieve their consensus goal to provide long-term protection, is unknown. We propose that this resembles an ecosystem based on collective behaviour, and aim to establish by which mechanism the diverse CD8 T cell clones coexist at the initiation of an immune response. In particular, we will: 1) Define T cell inter-communication and co-influence. We will address the fate of diverse CD8 T cell clones when they are by themselves, or when they cohabit with each other.2) Define the environment that fosters CD8 T cell diversity. We will define the cellular composition in space and time of this environment, and whether this environment might triage recruited T cells.3) Define the relevance of a T cell ecosystem for the outcome of heterosubtypic immunity. Altogether, we expect the outcomes will improve our understanding of healthy CD8 T cell responses and ultimately bring new concepts to manipulate those responses. Vaccination is the best example of successful manipulation of the immune system, however, the control of some pathogens, like influenza. CD8 T cells are usually not triggered during vaccination, despite their importance for virus eradication. This project will provide a comprehensive characterisation of the mechanisms and environment necessary for the generation of a T cell ecosystem, and the benefits for immune responses.

大多数实体，如人类、动物或植物，都生活在一个群体、社会或生态系统中，并从中受益。例如，蜜蜂在找到食物来源时会互相通知，并将它们各自找到的所有食物都保存在蜂箱中，这对整个蜂群都有好处。这一提议是基于一种假设，即一些称为CD8 T细胞的白色血细胞在健康反应期间也会将自己组织成一个生态系统，这对整体结果是有益的。每个CD8 T细胞克隆都是独特的，因为它表达一种特异性T细胞受体，该受体识别具有不同亲和力的不同抗原组。有人提出，这种多样性是对病毒的长期免疫所必需的。尽管事实上一些CD8 T细胞具有竞争优势并且足以控制感染，但多样性仍然存在，这表明募集到应答的CD8 T细胞克隆的宽度受到积极调控。不同的T细胞克隆如何共存和交流以实现其共识目标，以提供长期保护，目前尚不清楚。我们提出，这类似于一个基于集体行为的生态系统，并旨在建立在免疫反应开始时，不同的CD8 T细胞克隆共存的机制。具体而言，我们将：1）定义T细胞相互通信和共同影响。我们将解决不同CD 8 T细胞克隆单独存在或相互共存时的命运。2）定义促进CD 8 T细胞多样性的环境。我们将定义这种环境在空间和时间上的细胞组成，以及这种环境是否可能对招募的T细胞进行分类。3）定义T细胞生态系统与异亚型免疫结果的相关性。总而言之，我们希望这些结果将提高我们对健康CD8 T细胞反应的理解，并最终带来操纵这些反应的新概念。接种疫苗是成功操纵免疫系统的最佳例子，然而，控制一些病原体，如流感。CD8 T细胞通常不会在疫苗接种过程中被触发，尽管它们对病毒根除很重要。该项目将提供T细胞生态系统生成所需的机制和环境的全面表征，以及免疫应答的益处。

项目成果

Spatiotemporal behavior of T cells in vaccination.

疫苗接种中 T 细胞的时空行为。

• DOI: 10.1016/j.biocel.2022.106224
• 发表时间: 2022
• 期刊: The international journal of biochemistry & cell biology
• 作者: Chiodetti AL

Imaging of In Situ Interferon Gamma Production in the Mouse Spleen following <em>Listeria monocytogenes</em> Infection

单核细胞增生李斯特菌感染后小鼠脾脏中原位干扰素γ产生的成像

• DOI: 10.3791/59819
• 发表时间: 2019
• 期刊: Journal of Visualized Experiments
• 作者: Gérard A

Photoswitchable gRNAs for Spatiotemporally Controlled CRISPR-Cas-Based Genomic Regulation

• DOI: 10.1021/acscentsci.9b01093
• 发表时间: 2020-05-27
• 期刊: ACS CENTRAL SCIENCE
• 影响因子: 18.2
• 作者: Moroz-Omori, Elena, V;Satyapertiwi, Dwiantari;Stevens, Molly M.
• 通讯作者: Stevens, Molly M.

Integration of Avidity and Differentiation is enabled by CD8 + T-cell sensing of IFN-?

CD8 T 细胞对 IFN-α 的感应可实现亲合力和分化的整合。

• DOI: 10.1101/2023.03.06.531375
• 发表时间: 2023
• 作者: Uhl L