Funding outcome

For children born with a heart problem at birth (or 'congenital heart disease'), about half of them will need a transplant despite advances in alternative surgical procedures. A major challenge in heart transplantation is rejection of the donor heart by the recipient. This is due to specific molecules that are present on cells of the heart that are unique to the donor. The recipient's immune system recognizes these molecules as foreign and tries to destroy the organ. Current treatment to prevent rejection consists of medications that decrease the recipient's immune response. However, these drugs cause many side-effects and make the person more prone to infections and cancer. A promising alternative strategy is to use special immune cells that naturally suppress immune responses, called 'regulatory T cells' (or 'Tregs'), as an anti-rejection cell therapy. Tregs arise in the thymus gland, a structure that is located in the chest. In children who have any heart operation, the thymus may be in the way for access to the heart and is therefore removed and discarded. We have previously shown that we can use these discarded thymuses to isolate large quantities of Tregs. In our new study, we will investigate whether Tregs that specifically suppress immune responses to donor molecules can be generated by growing them with immune cells from a donor. As the Tregs develop in the thymus, they will come into contact with the foreign donor molecules. We think that this will result in development of 'donor-specific' Tregs. If we take these Tregs and put them into a situation where the donor cells were being attacked by immune cells, the Tregs would suppress the immune cells from doing damage. Taking it to the big picture, this means that Tregs that have learned to 'protect' donor organ's surface molecules should be able to stop the recipient's immune system from attacking the organ. This may present us with a new therapy to tackle immune rejection in pediatric transplant recipients.