Reprogramming the immune system for graft tolerance
During organ transplantation, the immune system recognises the transplant as foreign and attacks it, often causing rejection. To overcome this, certain immunosuppressive drugs are given that aim to dampen the immune response against the donor organ. Although these medications are efficient in preventing or controlling early acute rejection or graft versus host disease short term, they have numerous side-effects including infections and kidney problems. Tailoring immunosuppression to patient needs according to the immune reactivity of each transplant would represent a significant advance in transplantation medicine, avoiding the side-effects of unnecessary drug administration. This represented the ultimate goal of the EU-funded ‘Reprogramming the immune system for the establishment of tolerance’ (RISET) project. To define molecular signatures of transplantation tolerance and rejection, researchers developed various diagnostic tools based on immunological measurements as well as genomic and proteomic assays. Validation of these tests and signatures is expected to implement them as immune monitoring tools in clinical trials and acceptable surrogate markers of graft acceptance. Additionally, by experimenting on pre-clinical models of tolerance, RISET project partners found that they could use dendritic cells (DCs) – the antigen presentation cells of our immune system – pulsed with allogeneic antigens as a means of inducing tolerance. Furthermore, transplantation of human regulatory T lymphocytes (T regs) is envisioned to promote tolerance in liver transplant recipients. Collectively, the RISET work holds enormous promise for organ transplantation as it provides novel insight for tolerance induction without the toxic conditioning regimens entailed by alternative protocols.