Allograft and xenograft unresponsiveness induced by transplantation of neonatal skin

Class I MHC-disparate skin allografts from neonatal donors survive longer than adult grafts in mice treated with antilymphocyte serum (ALS; days -1, +2) or ALS plus donor bone marrow cells (BMC; day +7 relative to grafting on day 0) or ALS, BMC, and a 2-week course of post-transplant CsA. We have now investigated whether this phenomenon extends to more strongly histoincompatible allografts (H2-KI and H2-KID mismatched) made to recipients treated with ALS, ALS plus BMC, or ALS, BMC, and CsA. Survival of neonatal grafts was longer than that of adult grafts in all experimental groups (P < 0.05). In ALS/BMC/CsA-treated mice, for example, median survival of neonatal C3H grafts was 46 days, with adult grafts surviving 22 days on C57BL/6 recipients (full MHC disparity). Survival of neonatal hamster skin grafted to B6AF1 mice was not augmented beyond that for adult skin using a similar immunosuppressive protocol. But if alternate day ALS and CsA injections were begun on day -5, and ALS and CsA continued as in the allograft models, a significant xenogeneic neonatal survival advantage was demonstrated. (Donor BMC had no graft-prolonging effect in the xenograft model.) Donor BMC significantly prolonged full MHC-mismatched grafts from newborn, but not adult donors in ALS-treated recipients. Also, addition of CsA to ALS/BMC treatment prolonged the survival of neonatal, but not adult grafts mismatched at KI or KID. These results indicate that the survival advantage of neonatal grafts in immunosuppressed recipients extends to strong allogeneic incompatibilities and even to a xenograft model.