Pretransplant intrathymic inoculation of donor antigen combined with FK506 treatment: prolongation of survival of cardiac, but not renal, allografts in rats.

Abstract

It has been shown that pretransplant intrathymic injection of donor antigen prolongs rat cardiac allograft survival. The purpose of the present study was to evaluate whether co-administration of FK506 could enhance the beneficial effect of intrathymic preimmunization; we also wished to clarify whether this combined treatment could be effective for renal allografts. Seven days prior to transplantation 5 x 10(7) donor splenocytes were injected into the thymus of LEW (RT1l) recipients of WKA (RT1u) cardiac or renal allografts. Using a miniosmotic pump, FK506 was administered for 7 days before transplantation at a dose of 3 mg/kg/day. Whereas intrathymic injection of donor splenocytes or subcutaneous FK506 alone showed limited (15.2 days) or no (7.3 days) prolongation of cardiac allograft survival, the combined treatment with these two modalities synergistically prolonged the survival of the cardiac allograft (> 82.0 days). This combined treatment, however, failed to prolong renal allograft survival (8.4 days). Although donor-specific prolongation of a second cardiac allograft was obtained in LEW rats with a well beating WKA heart, two of the three recipients ultimately rejected both first and second WKA cardiac allografts. Additionally, LEW rats with a long-surviving WKA heart rejected a WKA renal allograft in a normal fashion. These data demonstrate a synergistic effect of intrathymic injection of donor splenocytes and subcutaneous FK506 on cardiac, but not renal, allograft survival and suggest that quantitative or qualitative differences of immunogenicity of kidney may contribute to the rejection of renal allografts.