TOLERANCE TO EXPERIMENTAL CARDIAC ALLOGRAFTS PRODUCED BY NEONATAL INTRATHYMIC INJECTION OF DONOR CELLS

Intrathymic inoculation of allogeneic cells after systemic administrat ion of antilymphocyte serum in adult experimental animals has produced donor-specific tolerance to cardiac allografts. We investigated wheth er thymic injection of allogeneic cells without antilymphocyte serum i n neonatal Lewis rats (day 1 of life) with immature immune systems als o produced tolerance to cardiac grafts. Intrathymic or intraperitoneal injection of 5 x 10(7) Lewis (control) or Lewis-Brown Norway (allogen eic) spleen cells in Lewis neonates was followed by heterotopic cardia c transplantation using Lewis, Lewis-Brown Norway, or Wistar Furth (th ird-party allograft) hearts at 6 to 8 weeks of age. Graft survival was prolonged with both intraperitoneal and intrathymic allogeneic cells. Recipients of cells by the intrathymic route had longer graft surviva l, and 2 of 5 animals achieved permanent graft acceptance (longer than 100 days). As expected, Lewis isografts survived indefinitely, wherea s third-party Wistar Furth allografts were rejected in the usual time frame. Intrathymic introduction of allogeneic cells in a neonatal reci pient with an immature immune system can produce donor-specific tolera nce to a subsequent graft without the need for a systemic immunosuppre ssion regimen, even transiently