Abstract
The goal of immunosuppression in solid organ transplantation is to blunt the immune response of the patient to the allograft, while maintaining sufficient resistance to avoid opportunistic infections and malignancy. Despite progress in this field, rejection processes, particularly of the chronic form, remain an important cause of morbidity and graft loss. This review discusses the advances in drug development and pharmacology as well as in immunobiology, which are likely to lead to more potent, effective and selective regimens to improve the therapeutic efficacy and overcome the range of adverse side effects now plaguing the transplant enterprise. The future era of transplantation is likely to focus on receptor or cytosolic enzyme targets more specifically represented on or in lymphocytes as opposed to other cells or tissues. Four current targets of this strategy are: the chemokine receptor-7 surface marker that mediates lymphocyte affinity for specific types of high endothelial venules; Zap-70, a signaling enzyme associated with T cell antigen receptors (signal 1); plasma membrane proteins mediating costimulation (signal 2); and antagonists of Janus kinase 3 (Jak3), an enzyme transducing cytokine signals from the cell surface to the interior (signal 3).
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