NEONATAL INTRATHYMIC SPLENOCYTE INJECTION YIELDS PROLONGED CARDIAC XENOGRAFT SURVIVAL

Intrathymic (IT) injection of allogenic cells without administration o f anti-lymphocyte serum (ALS) in neonatal recipients has induced donor -specific tolerance to subsequent cardiac allografts in rats. This stu dy examines whether similar tactics can be successfully applied to a h amster-to-rat cardiac xenotransplantation model. Lewis neonates on the ir first day of life underwent IT, subcutaneous (SC), intraperitoneal (IP), or intravenous (IV) injections of 5 x 10(7) Golden Syrian hamste r splenocytes. After six weeks, the rats underwent heterotopic cardiac transplantation of hamster hearts. Cyclophosphamide (CyP) was adminis tered on the day before surgery and postoperatively to suppress antibo dy-mediated graft rejection. Rats given splenocytes with 80 mg/kg of C yP had the following graft survival times: 8 to 12 days for IT injecti on (mean, 9.4 days); 5 to 7 days for SC injection (mean, 6.6 days); 4 to 11 days for IP injection (mean, 7.4 days); and 4 to 13 days for IV injection (mean, 7.9 days). Only the extension of graft survival produ ced by IT injection was statistically significant in comparison with t he rats given only CyP treatment(mean, 7.5 days; P < 0.05). Thus, it a ppears that IT injection of xenogenic splenocytes in neonatal recipien ts 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 techniq ues.