A Modern View of Transplant Immunology and Immunosuppression

Transplantation is the treatment of choice for end-stage failure of various vital organs. The main issue, however, remains the need to suppress the host’s immune system in the long term to ensure prolonged survival of the graft. Despite T cell-directed medications significantly improved short-term allograft survival by reducing the incidence of acute cellular rejection, they had little effect in preventing chronic allograft dysfunction and prolonging long-term graft survival. Furthermore, long-term non-specific immunosuppression can cause life-threatening complications. Therefore, new strategies are being researched to minimize maintenance immunosuppression. These include the use of induction immunosuppressive therapy with T cell-depleting or non-depleting antibodies in the early days after transplantation alone or in combination with maintenance immunosuppression based on the costimulatory blocker belatacept. The ultimate goal is to induce donor-specific tolerance, which is defined as the absence of a destructive host immune response toward the allograft without the need for generalized immunosuppression. This is aimed at moving away from harmful immunosuppressive regimens and promoting long-term graft survival. Cell-based therapies such as hematopoietic stem cells, T regulatory cells, and mesenchymal stromal cells have mainly been explored in kidney transplantation but are now also being translated to other solid organ transplants. The initial results are encouraging, but more pre-clinical and clinical research is needed to address the many remaining questions surrounding this innovative technology, which is still some way off from becoming a standard treatment protocol in transplantation.