A novel pathway in the control of memory T cell function during immune responses to viral re-infection.

在病毒再次感染的免疫反应过程中控制记忆 T 细胞功能的新途径。

• 批准号: MR/V011243/1
• 负责人: Mark Travis
• 金额: $ 76.75万
• 依托单位: University of Manchester
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2021
• 资助国家: 英国
• 起止时间: 2021 至 无数据
• 项目状态: 未结题
• 来源: https://gtr.ukri.org/projects?ref=MR%2FV011243%2F1
• 关键词: novel; pathway; control; memory; cell

When we are infected with a microbe such as a virus for a second time, we deal with it faster and more efficiently than the first time. This occurs because of a phenomenon called immunological memory, and is the cornerstone of how vaccinations protect us. Crucial cells underpinning this better immune response are memory T cells. However, we do not understand how these cells are controlled to fight off infections quickly and effectively, but not cause harm to our own bodies in the process.Our recent work has identified a new pathway by which memory T cell responses are controlled. Using mouse models, we have discovered that certain types of memory T cell can limit how strong the immune response is during viral re-infection, via a molecule called TGF-beta. Removing this pathway experimentally appears to promote a more rapid response to re-infection. This raises many important questions that we will address in this project: How is the novel pathway controlled? In what way does it contribute to the immune response to viral re-infection? Is this pathway active in humans when re-infected with a virus? Together, work in this proposal will characterise this new phenomenon, increase our understanding of how immunological memory works and identify new potential ways of promoting more effective responses to viral infection.

当我们第二次被病毒等微生物感染时，我们处理它的速度和效率比第一次更快、更有效。这是由于一种被称为免疫记忆的现象发生的，也是疫苗如何保护我们的基石。支持这种更好的免疫反应的关键细胞是记忆T细胞。然而，我们不知道如何控制这些细胞来快速有效地抵御感染，而不是在这个过程中对我们自己的身体造成伤害。我们最近的工作发现了一条控制记忆T细胞反应的新途径。利用小鼠模型，我们发现某些类型的记忆T细胞可以通过一种名为转化生长因子-β的分子来限制病毒再次感染期间免疫反应的强度。从实验上看，移除这一途径似乎可以促进对再次感染的更快反应。这提出了许多重要的问题，我们将在这个项目中解决：如何控制新的途径？它以什么方式对病毒再次感染的免疫反应做出贡献？当人类再次感染病毒时，这一途径是否活跃？总之，这项提案将描述这一新现象的特征，增加我们对免疫记忆如何工作的理解，并确定促进对病毒感染做出更有效反应的新的潜在方法。

项目成果

Discovery of uncompetitive inhibitors of SapM that compromise intracellular survival of Mycobacterium tuberculosis.

• DOI: 10.1038/s41598-021-87117-x
• 发表时间: 2021-04-07
• 期刊: Scientific reports
• 影响因子: 4.6
• 作者: Fernández-Soto P;Casulli J;Solano-Castro D;Rodríguez-Fernández P;Jowitt TA;Travis MA;Cavet JS;Tabernero L
• 通讯作者: Tabernero L

How regulatory T cells are primed to aid tolerance of gut bacteria.

调节性 T 细胞如何启动以帮助肠道细菌耐受。

• DOI: 10.1038/d41586-022-03368-2
• 发表时间: 2022
• 期刊: Nature
• 影响因子: 64.8
• 作者: Travis MA

A subset of CD4+ effector memory T cells limit immunity to pulmonary viral infection and prevent tissue pathology via activation of latent TGFß

CD4 效应记忆 T 细胞的一个子集限制对肺部病毒感染的免疫力，并通过激活潜在的 TGFα 来预防组织病理学

• DOI: 10.1101/2023.03.02.527395
• 发表时间: 2023
• 作者: McEntee C

Group 2 Innate Lymphoid Cells Are Detrimental to the Control of Infection with Francisella tularensis.

• DOI: 10.4049/jimmunol.2100651
• 发表时间: 2023-03-01
• 期刊: JOURNAL OF IMMUNOLOGY
• 影响因子: 4.4
• 作者: Dow, Joshua;Cytlak, Urszula M.;Casulli, Joshua;McEntee, Craig P.;Smedley, Catherine;Hodge, Suzanne H.;D'Elia, Riccardo, V;Hepworth, Matthew R.;Travis, Mark A.
• 通讯作者: Travis, Mark A.