Neonatal Intrathymic Splenocyte Injection Yields Prolonged Cardiac Xenograft Survival

Intrathymic (i.t.) injection of allogenic cells without administration of anti-lymphocyte serum (ALS) in neonatal recipients has induced donor-specific tolerance to subsequent cardiac allografts in rats. This study examines whether similar tactics can be successfully applied to a hamster-to-rat cardiac xenotransplantation model. Lewis neonates on their first day of life underwent i.t., subcutaneous (s.c.), intraperitoneal (i.p.), or intravenous (i.v.) injections of 5 x 10(7) Golden Syrian hamster splenocytes. After six weeks, the rats underwent heterotopic cardiac transplantation of hamster hearts. Cyclophosphamide (CyP) was administered on the day before surgery and postoperatively to suppress antibody-mediated graft rejection. Rats given splenocytes with 80 mg/kg of CyP had the following graft survival times: 8 to 12 days for i.t. injection (mean, 9.4 days); 5 to 7 days for s.c. injection (mean, 6.6 days); 4 to 11 days for i.p. injection (mean, 7.4 days); and 4 to 13 days for i.v. injection (mean, 7.9 days). Only the extension of graft survival produced by i.t. injection was statistically significant in comparison with the rats given only CyP treatment (mean, 7.5 days; P < 0.05). Thus, it appears that i.t. injection of xenogenic splenocytes in neonatal recipients with administration of CyP, but without ALS, can prolong xenograft survival. This biological intervention may be most useful in pediatric xenotransplantation when combined with other immunomodulation techniques.