Transplant Tolerance: New Insights and Strategies for Long-Term Allograft Acceptance

Abstract

One of the greatest advances in medicine during the past century is the introduction of organ transplantation. This therapeutic strategy designed to treat organ failure and organ dysfunction allows to prolong the survival of many patients that are faced with no other treatment option. Today, organ transplantation between genetically dissimilar individuals (allogeneic grafting) is a procedure widely used as a therapeutic alternative in cases of organ failure, hematological disease treatment, and some malignancies. Despite the potential of organ transplantation, the administration of immunosuppressive drugs required for allograft acceptance induces severe immunosuppression in transplanted patients, which leads to serious side effects such as infection with opportunistic pathogens and the occurrence of neoplasias, in addition to the known intrinsic toxicity of these drugs. To solve this setback in allotransplantation, researchers have focused on manipulating the immune response in order to create a state of tolerance rather than unspecific immunosuppression. Here, we describe the different treatments and some of the novel immunotherapeutic strategies undertaken to induce transplantation tolerance.

Generation of suppressive blood cells for control of allograft rejection

“…Donor-derived leucocytes rendered apoptotic prolonged heart allograft survival in mice when injected into recipients before transplantation (reviewed by [1]). Bittencourt et al [17] showed that injection of apoptotic donor SPCs into mice enhances bone marrow engraftment independently of the origin of cells.…”

“…Enormous efforts have been made in organ transplantation for the development of therapies which lead away from general immunosuppression towards donor-specific inhibition of the immune response [1]. Current strategies for induction of clinically relevant immunologic tolerance are based on inhibition or depletion time-consuming procedures, factors which limit their application in clinical routine.…”

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“…The secretion of cytokines leads to the initiation of immune response including inflammation, activation of pro inflammatory cells and proliferation of T and B cells [19]. While the exact mechanisms of rejection are not yet fully known, what is known is that the production of these cytokines and other alloantibodies cause activation of the complement system [20][21][22]. Activation of the complement system causes inflammation and further activation of the immune system, thus leading to damage of the transplanted organ [20][21][22].…”

Home-Grown Kidneys: Challenges and Mechanisms Behind Tissue Engineering for the Treatment of Chronic Kidney Disease

“…19 While the exact mechanisms of rejection are not yet fully known, what is known is that the production of these cytokines and other alloantibodies cause activation of the complement system. [20][21][22] Activation of the complement system causes inflammation and further activation of the immune system, thus leading to damage of the transplanted organ.…”