Regulation of T cell differentiation by stimulation strength

点击翻译按钮获取中文摘要

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.