title: The requirement for the renal transplant to induce allograft unresponsiveness by the combination of extracted histocompatibility antigen and cyclosporine.
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 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.
mesh_terms: D000818:Animals; D003524:Cyclosporins / Q000008:administration & dosage*; D006649:Histocompatibility Antigens / Q000008:administration & dosage*; D007165:Immunosuppression Therapy / Q000379:methods*; D007668:Kidney / Q000276:immunology; D016030:Kidney Transplantation; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D013156:Splenectomy; D050378:T-Lymphocytes, Regulatory / Q000276:immunology; D013997:Time Factors
chemical_list: D003524:Cyclosporins; D006649:Histocompatibility Antigens