RESUMEN
Modern immunosuppression drug regimens have produced excellent short-term survival after liver transplantation but it is generally accepted that the side effects of these medications remain a significant contributing factor for less satisfactory long term outcomes. The liver has unique tolerogenic properties as evidenced by the higher rates of operational tolerance seen in liver transplant recipients compared to other solid organ transplants, and therefore, liver transplantation offers an attractive setting in which to study tolerizing therapies. CD4+ CD25+ FOXP3+ regulatory T cells (Tregs) are crucial for maintenance of self-tolerance and prevention of autoimmune disease and are therefore an appealing potential candidate for use as a tolerizing cell therapy. In this review, we summarize the evidence from drug withdrawal trials of spontaneous operational tolerance in liver transplantation, the unique immunology of the hepatic microenvironment, the evidence for the use of CD4+ CD25+ FOXP3+ regulatory T cells as a tolerance inducing therapy in liver transplantation and the challenges in producing clinical grade Treg cell products.
Asunto(s)
Trasplante de Hígado/métodos , Linfocitos T Reguladores/inmunología , Animales , Tratamiento Basado en Trasplante de Células y Tejidos/métodos , Ensayos Clínicos como Asunto , Humanos , Terapia de Inmunosupresión/métodos , Inmunosupresores/administración & dosificación , Hígado/inmunología , Tolerancia al TrasplanteRESUMEN
Current immunosuppression regimens in liver transplantation provide excellent short-term survival rates but have many deleterious long-term side effects. They are therefore associated with the higher mortality and morbidity seen in liver transplant recipients compared to the general population and the notion that many liver transplant recipients are over-immunosuppressed is widely accepted. Liver allografts show a greater resistance to alloimmune responses than other solid organ transplants and recent research suggests up to 60% of highly selected recipients could wean off immunosuppression completely. In this review, we look at the evidence from immunosuppression withdrawal trials, the potential benefits of immunosuppression withdrawal and the identification of tolerant transplant recipients.