The three‐signal hypothesis of lymphocyte activation/targets for immunosuppression

Kidney transplantation is the preferred mode of renal replacement therapy for most patients with end-stage renal disease. Despite the increasing success of transplantation over the years, allograft rejection remains a major problem. Recently, there has been considerable improvement in understanding the role of the immune system in rejection. In the setting of transplantation, T cells have proved to be crucial players in the immune response, and their activation has been shown to be a very tightly regulated process involving numerous interactions of receptors including the T-cell receptor (TCR):CD3 complex, co-stimulatory receptors, and appropriate signaling molecules, resulting in production of cytokines as well as clonal expansion and differentiation of effector T lymphocytes. In this review, current knowledge of the mechanisms of lymphocyte activation as well as potential targets for various immunosuppressive agents are discussed.