[Immunological tolerance and liver transplantation]

The induction of tolerance to allografts has traditionally been one of the basic aims of transplantation research. Multiple data obtained in experimental models indicate that the outcome of transplantation (rejection versus acceptance/tolerance) depends on the balance between allo-reactive cytopathic lymphocytes and immunoregulatory lymphocytes. Thus, most tolerance-inducing treatments aim to reduce the number of allo-aggressive lymphocytes and, at the same time, to increase the population of regulatory lymphocytes, which ensure graft viability once drug therapy has been withdrawn. Liver allografts are singular in that they are accepted without the need for treatment in most experimental models. Likewise, in humans, liver grafts also show a lower susceptibility to rejection than any other organ and immunosuppressive treatment can be completely eliminated in approximately 25% of recipients. Many mechanisms have been proposed to explain the tolerogenic properties of the liver. Notable among these are the effects derived from the large number of passing leukocytes present in the liver and its peculiar anatomy that maximizes contact among blood lymphocytes and liver cells with tolerogenic potential. Although there are many cases of tolerance in human allograft recipients, therapeutic strategies that would allow predictable tolerance induction and without a high risk of adverse affects are still lacking. Therefore, most studies in humans have traditionally aimed to minimize doses of immunosuppressive drugs rather than eliminate them. However, recent results in preclinical models and pilot studies indicate that therapeutic protocols for tolerance induction may become available in the not too distant future.