DIFFERENT IMMUNE EFFECTS ON CARDIAC ALLOGRAFTS AND XENOGRAFTS INDUCEDBY NEONATAL INTRATHYMIC INOCULATION WITH ALLOGENEIC AND XENOGENEIC ANTIGENS

Background: In a previous study we demonstrated that intrathymic expos ure of neonatal rats to both alloantigens and xenoantigens produced to lerance only to subsequent cardiac allografts and not to xenografts im planted when the animals were 6 weeks old. Interestingly, graft recipi ents were not sensitized to the xenografts as observed in the adult mo del. This study was designed to investigate whether earlier grafting w ould produce tolerance to cardiac xenografts in animals pretreated by neonatal intrathymic inoculation with allogeneic and xenogeneic cells. Methods: All recipient animals were Lewis rats. Donors were either Le wis Brown Norway rats or Golden Syrian hamsters. Lewis Brown Norway ra t and hamster splenocytes (25 x 10(6) cells in a volume of 0.01 ml) we re inoculated percutaneously into the thymus of neonatal recipients (n = 22). At age 4 weeks, five pretreated recipients underwent cervical heterotopic heart transplantation with rat hearts, and 2 weeks later a bdominal heterotopic transplantation was done with hamster donors. A s econd group (n = 6) received hamster hearts as the first graft and the n grafts from rat donors. The third group underwent rat followed by ha mster heart transplantation at age 6 to 7 weeks. Results: Mean rat all ograft survival time for groups 1, 2, and 3, respectively, was 49.8 da ys with 4 of 5 surviving indefinitely, 43.3 days with 2 of 3 surviving indefinitely, and 42 days with 7 of 11 surviving indefinitely (p < 0. 01 versus untreated control animals, 7.8 days, n = 5). In rats undergo ing transplantation at 4 weeks, cardiac xenografts were rejected in 2. 5 days and 2.3 days, which was significantly shorter than xenograft su rvival (3.3 days) in rats that underwent transplantation at an older a ge (p < 0.02), in naive rats (p < 0.05), and in rats treated with hams ter cells alone (p < 0.05). Mixed lymphocyte reaction showed a diminis hed proliferative response to Lewis Brown Norway rat cells in pretreat ed rats, which retained the ability to respond in culture to hamster c ells (p < 0.05). Conclusions: Earlier grafting in rats pretreated as n eonates produces allograft tolerance but may accelerate rejection of x enografts. Preliminary mixed lymphocyte reaction results suggest that only the alloimmune cellular proliferative response is abrogated by th is pretreatment.