Cellular immunotolerance in the transplant

In humans, a state of operational tolerance has been observed in some recipients who anecdotally or experimentally abandoned their immunosuppressive treatment. Besides, advances in the understanding of the immune response and the continuous appearance of new biological molecules have boosted the growing interest in transferring the knowledge concerning immune tolerance from experimental models to clinical transplantation. Most of the strategies for inducing tolerance target the T-lymphocytes, especially T CD4(+) since they play a central role in the regulation of the immune response. However, an effective tolerogenic treatment must also take into account the role of alloantibody producing B-lymphocytes, which have been shown to play a fundamental role in chronic rejection phenomena. There are multiple regulation and silencing mechanisms that operate both during lymphocyte ontogeny in the bone marrow and thymus (central tolerance) and in the periphery (peripheral tolerance). These regulatory mechanisms include the destruction of APCs by cytotoxic lymphocytes, suppressive cytokines, and activation-induced cell death, among others. However, the mechanism that in recent years has come to be attributed the greatest role has been the active suppression of the response by T-lymphocytes themselves. These lymphocytes are named as regulatory T cells that include Tregs CD4(+)CD25(+), Tr1 cells and Th3. The great therapeutic potential of regulatory lymphocyte populations for the control of allogeneic rejection is evident and several clinical trials in humans have been started to be implemented using populations of both Tregs and Tr1 cells for the prevention of allogeneic reactions.