THE REQUIREMENT FOR THE RENAL TRANSPLANT TO INDUCE ALLOGRAFT UNRESPONSIVENESS BY THE COMBINATION OF EXTRACTED HISTOCOMPATIBILITY ANTIGEN AND CYCLOSPORINE

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Abstract
The impact of the presence of the allograft on the induction of unresponsiveness by the immunosuppressive combination of cyclosporine (CsA) and 3M KCl-extracted histocompatibility Antigen (Ag) was assessed by comparing the outcome of renal transplants when the regimen was used pretransplantation versus peri- and posttransplantation. WFu rat hosts, which had been pretreated with either one (-11, −10, −9) or three (-25, −24, −23, −18, −17, −16, −11, −10, −9) cycles of CsA and BUF Ag (-11 or −25, −18, −11) prior to implantation of BUF renal allografts, failed to display the prolonged graft survival achieved with this regimen administered in the peri- (-1, 0, +1) and immediate posttrans-plant (+7, 8, 9, 14, 15, 16) period. However, OX-8 positive, putative T-suppressor (Ts) cells in the spleens of pretreated hosts were able to transfer slightly prolonged BUF allograft survival to virgin, secondary syngeneic hosts. The OX-8-positive cells induced by pretreatment were apparently inhibited from prolonging BUF allografts in primary hosts by cellular elements vulnerable to splenectomy, total-body irradiation, or a three-day peritransplant course of CsA therapy. Therefore the presence of the renal graft at the time of periand immediate posttransplant administration of Ag-CsA facilitates the induction of unresponsiveness, possibly due to continued release of histocompatibility antigen to stimulate, and/or to providing an important peripheral environment promoting differentiation and maturation of, Ts cells.