Forty years of publication of transplantation proceedings--the second decade: the cyclosporine revolution.
With surgical tools in place, increased knowledge concerning immunogenetics and alloimmunity as well as improved management of immunocompromised patients, the foundations were lain for the rapid development of the transplantation enterprise. In contrast to pre-transplant conditioning by thoracic duct drainage or total lymphoid irradiation, which were too cumbersome for routine execution among the burgeoning recipient pool, cyclosporine was a facile method to produce immunosuppression de novo after transplantation. On the one hand, clinical data confirmed the potency of cyclosporine in a variety of clinical settings. On the other hand, a pleiotropic array of side effects, particularly nephrotoxicity, beclouded the regimens, even when used in reduced doses in combination with azathioprine or together with rigorous individualization of therapy by concentration control. The advent of cyclosporine condemned conditioning by pretransplant blood transfusions and donor-recipient HLA matching to therapeutic obsolescence. However, cross-matching achieved greater significance particularly due to the development of flow cytometry methods to detect modest amounts of anti-donor antibody. Adjunctive treatments with polyclonal preparations or monoclonal antibodies were developed to provide an additional layer of security during the critical induction phase of immunosuppression and for treatment of rejection episodes refractory to high dose steroid therapy. Active immunologic investigation was stimulated by antibodies that discriminated CD4+ versus CD8+ T cells, leading to dissection of their numbers of precursors or mature elements as well as their distinct activities. The search for methods to induce, maintain and detect the state of transplantation tolerance continued. The encouraging results in clinical transplantation raised a variety of ethical concerns related to public attitudes; to retrieval, distribution, and allocation of the limited supply of deceased donor organs; the increased utilization of living persons; the opportunities for commerce; the quasi-righteous requests for organ gifts by unrelated individuals and the scant financial resources for long-term treatment with costly immunosuppression. Transplantation had now achieved its rightful place in the clinical armamentarium.
Kahan
Barry D
BD
Division of Immunology and Organ Transplantation, The University of Texas-Health Science Center at Houston Medical School, Houston, Texas 77030, USA. Barry.D.Kahan@uth.tmc.edu
D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D002986:Clinical Trials as Topic; D016572:Cyclosporine / Q000009:adverse effects / Q000266:history / Q000627:therapeutic use*; D006084:Graft Rejection / Q000517:prevention & control; D049673:History, 20th Century; D049674:History, 21st Century; D006801:Humans; D007668:Kidney / Q000473:pathology; D010506:Periodicals as Topic / Q000266:history*; D016559:Tacrolimus / Q000266:history / Q000627:therapeutic use; D014180:Transplantation / Q000266:history*; D014181:Transplantation Immunology
D016572:Cyclosporine; D016559:Tacrolimus