The induction of active or peripheral tolerance in organ transplantation: dream or reality

Immunological tolerance induction is one of the most exciting research fields in experimental and clinical transplantation. From the first discovery of Nobel Prize awarded to L. Brent and P. Medawar, beside the classical induction of central tolerance in newborn mice, several methods, interventions and compounds have been introduced with a view to establishing tolerance. It was clarified that the mechanisms have different characteristics for central and peripheral or active/operative transplantation tolerance. In the case of the latter, tolerance was accompanied with mixed chimeric state. In the last decade, new compounds, such as monoclonal antibodies specific for membrane receptors on T- and APC cells responsible for signal 1 and signal 2 functions have been employed to induce operative tolerance. Among various methods and immunosuppressive interventions, non-myeloablative treatments combined with hematopoietic stem cell infusion showed the most effective results. This form of induction is associated with the well known "beneficial transfusion effect" in kidney transplantation. Based on the experimental achievements of clinical organ transplantation, various protocols have been introduced to induce peripheral tolerance. In spite of the short observation time of this progress the results seem to be promising, first of all, in the prolonged rejection-free survival time of the graft and the possibility to withdraw the immunosuppressive treatment altogether.