Inhibition of acute rejection after skin or cardiac transplantation by administration of donor antigens in the rat.

Abstract

We examined differences in host immunologic changes induced by the intravenous or intraportal administration of donor antigens at engrafting and evaluated their contribution to graft survival using a rat transplantation model. Lewis rat recipients were given either an intravenous or intraportal injection of donor splenocytes (1 x 10(8)) immediately after receiving skin grafts from Brown Norway donors. The immunologic responses were analyzed by mixed lymphocyte reaction (MLR) and profiles of interferon-Gamma, interleukin (IL)-2, and IL-10 in MLR supernatants. The effect on cardiac transplantation of perioperative administration of low-dose FK506 (0.1 mg/kg per day) was also examined. Mixed lymphocyte reactions using splenocytes and sera from recipients treated intraportally were greatly inhibited. Interferon-gamma, IL-2, and IL-10 levels were significantly higher after intraportal treatment compared with intravenous treatment (P < 0.05). When FK506 was injected from day 3, a significant enhancement of cardiac allograft survival was demonstrated by intraportal treatment (16.1 +/- 2.9 days) in comparison to the non-treatment (13.0 +/- 1.7 days, P < 0.05) and intravenous treatment rats (11.7 +/- 2.7 days, P < 0.05). The Th2 deviation induced with intraportal alloantigen administration immediately after engraftment was thus observed to produce a synergistic effect with immunosuppressant treatment to suppress acute rejection.