Grant: Operating Grant

A central idea in immunology is that an infection must stimulate the immune system to make special cells called memory T cells. As the name implies, these cells remain in the body for the life of the individual and when the same infection is encountered, these memory T cells generate a strong immune attack to prevent the infection from taking hold. In fact, this is the basis of vaccines and is arguably one of the most successful achievements in modern medicine. Yet the precise way memory T cells are made and ways to improve the function of these immune cells remain unknown. Using our initial CIHR-funded grant, we developed a new mouse model to study the factors that are necessary to generate memory T cells. We genetically removed a gene called Atg5, an essential gene for a normal cell survival program called autophagy. Immune cells lacking Atg5 failed to survive through an infection and subsequently do not go on to produce memory T cells. We showed that immune cells that cannot survive in the absence of Atg5 display abnormal metabolism. Because metabolism is the most fundamental process of a cell, we believe this is the reason why immune cells cannot survive to become memory cells. The purpose of this proposal is to investigate how autophagy controls metabolism and the survival of T cells during an immune response. We also plan to examine whether there is a role for autophagy in controlling memory responses to human vaccines. This is an important step forward that will provide fundamental knowledge on the key events that shape memory T cells. The need for additional effective vaccines highlights the far reaching implications of our work and how to best to exploit the immune system to develop more effective immune responses and vaccines against human diseases like HIV/AIDS and cancer.