Maintenance Immunosuppression in Kidney Transplantation

Maintenance immunosuppression is essential to decrease the risk of transplant rejection and prolong the long-term viability of an allograft. Immunosuppressive agents target T-cell activation at different signaling stages. Signal 1 involves interaction of T-cell receptor major histocompatibility (MHC) and antigen. Signal 2 involves interaction of costimulatory molecule CD28 on T-cell with C80/86 on antigen-presenting cells. Signals 1 and 2 together through calcium-dependent calcineurin pathway, RAS-mitogen-activated protein kinase pathway, and nuclear factor-κβ pathway lead to IL-2 production and other cytokines. Signal 3 is the downstream activation resulting in T-cell proliferation and amplification through binding of IL-2 to its receptor activating mammalian target of rapamycin (Fig. 10.1) [1, 2].