Project 172511

The overall objective of our project is to understand why the body damages the blood vessels in Kawasaki disease (KD), the leading cause of acquired heart disease in Canadian children. An infection starts KD. An infection-triggered immune response directed against our own bodies is a common theme in autoimmune disease. In a healthy person, the cells, especially the T-cells, in the immune system die and the immune response turns off after an infection. In a person with autoimmune disease the cells of the immune system do not die and keeping going and attack parts of our own body. We have evidence that co-stimulation signals, molecules that are important in activating and keeping T-cells alive, are the key to helping T-cells escape death. This project will determine how co-stimulation rescues T-cells. We have developed an animal model which looks and acts like KD in children. We will use this model to answer our questions and apply what we learn to better understand the disease in children with KD. We will determine what governs the expression of co-stimulatory molecules associated with development of disease and why this leads to coronary heart disease in children. Not only will our work challenge existing paradigms and open a new chapter in autoimmune disease research, but have important implications for improving therapy of affected children.