Grant: Operating Grant

Severe heart disease in infancy leads to significant disability or death; neonatal heart transplantation is effective treatment. To prevent rejection of a heart transplant, immunosuppressive drugs need to be administered for the patient's lifetime. We are researching ways in which a heart transplant recipient may accept a transplanted heart without the need for life-long drug treatment. The acceptance of a transplant without the need for drug treatment is called transplantation tolerance. Transplant tolerance is a way that the immune system is taught to accept a transplant as 'self' while at the same time protecting from infection and disease. It was shown more than 50 years ago that the newborn immune system of laboratory mice was especially susceptible to the induction of tolerance to skin transplants. In our laboratory we study neonatal tolerance to heart transplants in mice, a powerful tool to ask questions that would be impossible to study in human infants. Our research group showed that this also occurs in humans. In this research project we will use our newborn mouse model to study in detail the events leading to heart transplant acceptance. For instance, we will explore the earliest events that occur following neonatal treatment by using special microscopes and fluorescent dyes. We will track the fate and determine the types of cells that are involved in inducing tolerance. We showed previously that tolerance also occurs in human infants but there is inadequate understanding of the mechanisms involved. Through this project, new knowledge will be generated which may allow expanded applications of tolerance in the clinical setting.