INDUCTION OF TOLERANCE TO AN EXPERIMENTAL CARDIAC ALLOGRAFT THROUGH INTRATHYMIC INOCULATION OF CLASS-II MAJOR HISTOCOMPATIBILITY COMPLEX DISPARATE ANTIGENS

Indefinite donor-specific tolerance to a cardiac allograft can be indu ced through pretransplantation intrathymic injection of donor spleen c ells and a single intraperitoneal injection of antilymphocyte serum, T his study was designed to determine whether this phenomenon was reprod ucible with grafts differing in either class I major histocompatibilit y complex only or class II MBC only, Donors of cells and hearts in all experiments were RP rats, Class I MHC disparate grafts were performed by placing an RP heart into a Lewis recipient, and class II disparate grafts were performed with RP donors and Wistar Furth recipients, Lew is (n = 10) and Wistar Furth (n = 10) recipients underwent intraperito neal injection of 1 mi antilympocyte serum and intrathymic injection o f 5 x 10(7) RP spleen cells, Three weeks later, heterotopic cardiac tr ansplantation was done with a heart from an RP rat, Control rats had n o pretreatment or received antilympocyte serum alone, Without pretreat ment, RP hearts survived 7 to 9 days (mean 8 days) in Lewis recipients (n = 5) and 9 to 14 days (mean 12 days) in Wistar Furth recipients (n = 5), Antilymphocyte serum alone produced slight prolongation of graf t survival, Lewis rats pretreated with class I disparate RP splenocyte s and antilympocyte serum had graft survivals of 8 to 27 days (mean 14 days), not significantly different from the results with antilympocyt e serum alone, Class II disparate RP grafts placed in pretreated Wista r Furth rats had significant prolongation of graft survival, with four of five grafts surviving longer than 60 days (p < 0.01 vs antilympocy te serum alone), These results suggest that a disparity at the class I I locus of the major histocompatibility complex is critical for the in duction of cardiac allograft tolerance after intrathymic inoculation o f allogeneic cells.