INDUCTION OF TOLERANCE IN RODENT CARDIAC ALLOTRANSPLANTATION USING ANMHC CLASS I-DERIVED PEPTIDE AND CYCLOSPORINE-A

Background. The synthetic peptide corresponding to residues 75-84 of t he human major histocompatibility complex class I molecule HLA-B7 (All otrap 07) has been shown to inhibit differentiation of cytotoxic T lym phocyte precursors. Subsequent treatment of LEW-1A rats with this pept ide was associated with a reduction in the level of cytotoxic activity directed to donor alloantigens. This study was undertaken to investig ate the effect of Allotrap 07 on rodent heart allograft survival in LE W-1A recipients. Methods. Heart allografts from Lewis rats were hetero topically transplanted into the infrarenal abdominal aorta of ACI reci pients. The treatment groups consisted of different regimens of short- term intravenous Allotrap 07 and oral cyclosporin A. All grafts were p alpated daily, with rejection defined as the cessation of palpable con tractions. Results. Cardiac allografts transplanted from Lewis to ACI rats survived indefinitely after administration of intravenous Allotra p 07 and oral cyclosporin A. Tolerance induction was donor-specific be cause third-party Brown-Norway, but not Lewis, grafts were rapidly rej ected after implantation into ACI recipients. Conclusions. Because don or-specific tolerance persisted long after cessation of peptide admini stration and did not occur when cyclosporin A was omitted from the imm unosuppressive regimen, the mechanism may involve induction of clonal anergy. (C) 1998 by The Society of Thoracic Surgeons.