Preventing unwanted immune responses and heart transplant rejection

Modulation of T cell function by proton channels: exploring a new route to ‘manageable’ immunosuppression

The only way to cure severe heart failure is a heart transplant, but the transplant can fail if someone’s immune system rejects the new organ. Research that reveals more about how the immune system is involved in rejection could reveal new ways to prevent the body rejecting precious donor hearts in the future. A protein called voltage-gated proton channel 1 (Hv1) is found in white blood cells which are part of our immune system. Professor Federica Marelli-Berg from Queen Mary, University of London, has found that T cells, a type of white blood cell, need Hv1 to become activated and travel to where they are needed. They also found that mice without Hv1 do not reject skin transplants very efficiently because their T cells do not function properly, and they do not develop infections or cancer (complications that can occur when people are given drugs to prevent rejection of a transplant). The BHF has awarded Professor Marelli-Berg a grant to find out how Hv1 works in immune responses governed by T-cells, and what effect Hv1 has on T cell activation and migration in mice. There are currently no drugs available to block the activity of the Hv1 molecule, so they will also generate an antibody that can block the Hv1 molecule. This antibody could become a new drug to regulate unwanted immune responses after a heart transplant and may have fewer side effects than current treatments.