Successful experimental heart transplantation without immunosuppressive drugs

Donor-specific unresponsiveness is an important goal of heart transplantation research. Work by other investigators has shown that intrathymic transplantation of pancreatic islet cells not only leads to factor permanent acceptance of the intrathymic graft but tolerance to subsequent extrathymic islet cell transplants. We applied this concept to a model of heart allotransplantation in the rat. Recipient Lewis rats were treated with 1 ml of antilymphocyte serum and 5 x 10(7) Lewis-Brown Norway spleen cells injected into the thymus under direct vision. Twenty-one days later, heterotopic heart transplantation was performed with Lewis-Brown Norway (allograft) and Wistar-Furth (third-party allograft) donors. Control Lewis recipients received no treatment, antilymphocyte serum alone, or antilymphocyte serum plus intrathymic syngeneic Lewis spleen cells. Another group of animals received intravenous Lewis-Brown Norway cells before transplantation with Lewis-Brown Norway heart donors. Untreated control animals had heart graft survival of 6 to 10 days (mean, 7.6 days) and 7 to 9 days (mean, 7.8 days) for Lewis-Brown Norway (n = 5) and Wistar-Furth (n = 5) donors, respectively. Antilymphocyte serum alone (n = 10) failed to prolong survival of Lewis-Brown Norway grafts (mean, 10.7 days; p = not significant). Antilymphocyte serum plus intrathymic Lewis cells (n = 5) did not prolong survival of a subsequent Lewis-Brown Norway graft (mean, 9.2 days; p = not significant). Survival of Wistar-Furth third-party allografts (n = 10) was not prolonged by intrathymic Lewis-Brown Norway cells (mean survival, 13.9 days; p = not significant).(ABSTRACT TRUNCATED AT 250 WORDS)