Prolongation of Rat Renal Allograft Survival by Cyclophosphamide and Intravenous Donor-Specific Antigens

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Abstract
Specific immunological hyporeactivity to Ag-B incompatible rat renal allografts was achieved after pretreatment of the recipients with donor strain platelets or spleen cells and cyclophosphamide (CY). The longest survival times were observed in animals pretreated with a single 75 mg/kg dose of CY together with 2 .times. 1010 donor strain platelets or 2.5 .times. 109 spleen cells i.v., 2 wk prior to kidney transplant (median survival time, 71 and 47 days, respectively, compared to 12 days in untreated rats). CY or antigen given alone were ineffective. Anti-donor antibody activity was routinely detectable in graft-bearing animals. Cell-mediated anti-donor immunity, although impaired, was still present in long-term survivors. Preservation of graft function and prolonged survival in antigen-CY-pretreated animals may be abetted by a combination of mechanisms including antigen-induced immunological enhancement, and deletion by CY of potentially reactive lymphoid cell clones. The use of CY in conjunction with donor antigen pretreatment may provide an additional increment of specific immunosuppression in clinical organ transplantation.

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