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

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.