Regulation of T cell differentiation by stimulation strength

通过刺激强度调节 T 细胞分化

• 批准号: MR/W016303/1
• 负责人: Arianne Richard
• 金额: $ 180.71万
• 依托单位: Babraham Institute
• 依托单位国家: 英国
• 项目类别: Fellowship
• 财政年份: 2022
• 资助国家: 英国
• 起止时间: 2022 至 无数据
• 项目状态: 未结题
• 来源: https://gtr.ukri.org/projects?ref=MR%2FW016303%2F1
• 关键词: Regulation; cell; differentiation; stimulation; strength

The immune system defends the body against infections. It is made up of a collection of specialised cells that fight infection in different ways. CD8 T cells are a type of immune cell that can find and kill virus-infected cells. When a T cell first encounters a harmful invader, it is stimulated to multiply, and its "daughter" cells specialise further to perform different functions. Some cells fight the current infection, while others become "memory" cells that provide defence against the same infection in the future. Previous research has shown that the strength of T cell stimulation in this initial encounter affects how the daughter T cells specialise. Many questions remain about how this occurs. In this proposal, I will answer these questions by investigating how T cells make decisions about the type of specialised responses they will develop. To do this, I will compare T cells after strong versus weak virus stimulation and use state-of-the-art techniques to examine which genes are turned on and off within individual cells. I will also examine how movement within lymph nodes and interactions with other types of immune cells impact this process. Finally, I will compare daughter cells that developed after strong stimulation versus those that developed after weak stimulation and test how well they fight a repeat infection. These data will reveal how T cells control their responses to provide the right balance of protection against current and future threats.This work will improve understanding of a fundamental process of the immune system and is also relevant for the design of therapies that aim to manipulate T cell responses. For example, long-lasting T cell memory is an important target of vaccination, and understanding how these responses develop may benefit vaccine design strategies. As the project will reveal fundamental properties of immune cell activity, it may also influence work in other fields of immunology including cancer immunotherapy and autoimmune disease research.

免疫系统保护身体免受感染。它由一组特殊的细胞组成，这些细胞以不同的方式对抗感染。CD8 T细胞是一种能够发现并杀死病毒感染细胞的免疫细胞。当T细胞第一次遇到有害的入侵者时，它会被刺激繁殖，而它的“子”细胞则会进一步特化以执行不同的功能。一些细胞对抗当前的感染，而另一些细胞则成为“记忆”细胞，为将来的相同感染提供防御。先前的研究表明，T细胞在初次接触时受到的刺激强度会影响子T细胞的分化。关于这是如何发生的，仍然存在许多问题。在这个提议中，我将通过研究T细胞如何决定它们将产生的特殊反应类型来回答这些问题。为了做到这一点，我将比较T细胞在强和弱病毒刺激后的表现，并使用最先进的技术来检查单个细胞内哪些基因是开启和关闭的。我还将研究淋巴结内的运动以及与其他类型免疫细胞的相互作用如何影响这一过程。最后，我将比较强刺激后产生的子细胞和弱刺激后产生的子细胞，并测试它们抵抗重复感染的能力。这些数据将揭示T细胞如何控制它们的反应，以提供针对当前和未来威胁的适当平衡保护。这项工作将提高对免疫系统基本过程的理解，也与设计旨在操纵T细胞反应的疗法有关。例如，持久的T细胞记忆是疫苗接种的一个重要目标，了解这些反应如何发展可能有利于疫苗设计策略。由于该项目将揭示免疫细胞活动的基本特性，它也可能影响其他免疫学领域的工作，包括癌症免疫治疗和自身免疫性疾病的研究。

项目成果

ChAdOx1 nCoV-19 vaccination generates spike-specific CD8+ T cells in aged mice.

ChAdOx1 nCoV-19 疫苗接种可在老年小鼠中产生尖峰特异性 CD8 T 细胞。

• DOI: 10.1111/imcb.12645
• 发表时间: 2023
• 期刊: Immunology and cell biology
• 影响因子: 4
• 作者: Foster WS