Project 466763

The COVID-19 pandemic has illustrated that elderly people are at much higher risk of developing severe symptoms from infection. This is partly due to reduced responsiveness of T cells, a type of immune cell that protects the body from foreign invaders, such as bacteria and viruses. It is known that T cell responses become less efficient with age, but whether changes to the immune environment in older people can impair T cell responses is incompletely understood. For T cells to effectively patrol all areas of the body, they are constantly commuting between different secondary lymphoid organs in which they can encounter infectious agents. T cells spend much of their time travelling along a network of roads within lymphoid organs created by fibroblastic reticular cells (FRCs). However, FRCs may become stiffer with age, which increases the amount of force they exert back on T cells. In response to greater external forces, cells increase the rigidity of their nucleus, which houses their genetic material. If cells cannot adapt to the higher pressure surrounding them, their genetic material will be damaged, causing them to lose their function. Consequently, T cells must adapt to different types of terrain to navigate efficiently and not harm any of their inner machinery. Although, as T cells age, they become ;rusty and may struggle with this adaptation. The goal of my research is to uncover how the structure and physical properties of FRC networks change with age and how aged T cells migrating through the network respond to these alterations. Understanding how T cells are affected by their environment will allow us to develop therapies that can restore immunity in older individuals and ultimately reduce the burden of infections and other diseases on the elder population.