Hijacking the immune system to help prevent heart transplant rejection

Optimising the efficacy of regulatory T cells: informing clinical application (renewal)

When the heart becomes irreversibly damaged and fails, heart transplantation can be the only treatment option. However rejection of the donor heart by the immune system is a major problem. Immunosuppressant drugs have unpleasant side effects, so new ways to help donor organs survive are needed. Our immune systems are made up of many different cells. Some fight infections and tumours. Some stop our body’s immune system reacting unnecessarily against our own tissues, such as regulatory T cells, or Tregs. One possible way to help donor organs survive is to ‘hijack’ Tregs, and use them as therapies to stop our bodies rejecting donor transplanted organs. With previous BHF funding, Professor Giovanna Lombardi and researchers at King’s College London have developed a new method of expanding Tregs in the lab, and tailoring them to recognise molecules on the transplant tissue, so they do not reject the organ. They tested if Tregs can prevent human cell or tissue transplant rejections using a new mouse model with a human immune system. They also developed a new scanning method to visualise Tregs. They will carry out the first ever Treg therapy trial in kidney and liver transplant patients later this year. But key questions remain about the safety and effectiveness of Tregs before they become a realistic treatment. Now the BHF has awarded a grant to the King’s researchers to find out if they can make Tregs even more effective at preventing transplant rejection. They will test if reducing inflammation, clotting or numbers of immune ‘B’ cells can improve the effectiveness of Tregs. They’ll use their scanning method to visualise where these engineered Tregs go in the body in mice, and further improve their new mouse model. This research will provide greater insight into the mechanisms of donor rejection and how Tregs could help. Ultimately, Treg therapy may help transplant recipients live longer with a better quality of life.