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

Transplant patients could soon receive infusions of their own immune cells to stop their bodies rejecting a donor organ, replacing lifelong daily doses of toxic immunosuppressive drugs. Organ transplantation saves lives, but the drugs that prevent rejection come with severe side effects—increased risk of infection, cancer, and organ damage. The immune system’s natural “regulatory T cells” (Tregs) can suppress rejection without those harms. This research group is about to start the first human trials of Treg therapy in organ transplant patients, but key questions remain about how to make the treatment safe and effective. The team will test five specific improvements: whether blocking the complement and coagulation cascades (blood-clotting pathways) boosts Treg function; whether depleting B cells (another immune cell type) helps; whether Tregs must control the direct immune response against the donor organ; whether engineering Tregs with chimeric antigen receptors (CARs) that recognise donor tissue makes them more potent; and whether using donor-specific Tregs avoids the blanket immune suppression caused by polyclonal cells. If successful, this work could transform transplant medicine—replacing broad immunosuppression with a targeted, living therapy that prevents rejection without the collateral damage. It could also inform Treg treatments for autoimmune diseases and bone marrow transplantation.