The requirement for the renal transplant to induce allograft unresponsiveness by the combination of extracted histocompatibility antigen and cyclosporine.

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 posttransplant (+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 peri and 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.