Development of clinical immunosuppression for organ transplantation.

The progress in the understanding of allograft rejection since the first modern kidney transplantation is enormous. The concept of the histocompatibility complex (HLA system) was born and the loci for the related genes are now identified. The actual structure of HLA antigens and the molecules (lymphokines) released by them are being understood. A population of lymphocytes (suppressor cells) which reduces the host immune response to tissue allografts has also been identified. With advanced understanding, ideas and methods for immunosuppression have been developed. Hyperacute rejection due to presensitization (secondary to preformed HLA antibody) ought to be avoided or attenuated, if it were to happen. The significance of previous blood transfusion or multiple pregnancies were clarified in this regard. The tests to determine such immunological reactivity were devised. Steroids, azathioprine and cyclosporine which are presently in use for immunosuppression were reviewed as to their actions, effects and side-effects. Total lymphoid irradiation presently appears as a potential effective immunosuppressive procedure and is currently being tried in certain transplant centers. The superiority of monoclonal antibodies against polyclonal antilymphocyte antibodies has been confirmed, although the latter also has various useful actions. Finally, the need and possible means to facilitate donor specific unresponsiveness are mentioned in perspectives for the future management of clinical organ transplantation.