Grant: Project Grant

Infants with severe heart disease often require transplants for survival. Without intervention, organ transplants are rejected by the recipient's immune system in a process that is complex and involves many cell types. To prevent rejection, transplant patients take powerful immunosuppressive drugs over their lifetime, which can lead to complications such as infections and cancer. Additionally, these drugs do not always successfully prevent rejection. We are searching for ways to "educate" the patient's immune system so that it can permanently tolerate the transplant without the need for immunosuppressive drugs. In the laboratory we study neonatal tolerance to heart transplants in mice, a powerful tool to ask questions that would not be feasible in human infants. In this research project we will deplete different cell types that are involved in rejection or that cause complications leaving behind the cells that induce tolerance. We will explore the earliest events that occur following depletion using special microscopes and fluorescent dyes. We will track the remaining cells and analyse their ability to induce and maintain tolerance. If successful such treatment will allow patients to accept their transplants with less need for immunosuppressive drugs. The technology would also be applicable to other types of transplants such as kidney.