Induction of allograft tolerance with neonatal skin

B6AF1 recipients treated with various combinations of ALS, CsA, and BMC were grafted with C3H skin from adult or neonatal donors. A survival advantage of neonatal skin compared with adult skin was clearly demonstrated in groups treated with ALS and CsA (median survival time [MST] = 89 days, neonatal skin; 50 days, adult skin), ALS and BMC, (MST = 92 days, neonatal; 64 days, adult skin), or with ALS only (MST = 55 days and 35 days, respectively). In these groups only neonatal grafts were observed to survive greater than 100 days. Also, once it was underway, rejection of the neonatal skin proceeded more slowly than that of adult skin. ALS/BMC/CsA treatment of adult skin recipients improved graft survival modestly (MST = 77 days, 20% of grafts surviving greater than 100 days). But neonatal graft survival was prolonged remarkably by the ALS/BMC/CsA treatment, with 95% of grafts surviving greater than 100 days and 84% surviving greater than 240 days. After bearing neonatal grafts for greater than 150 days, these mice were challenged with C3H adult skin grafts. The second grafts were uniformly accepted for greater than 135 additional days, but third-party grafts were rejected promptly. This specific tolerance could not be abrogated by injection of normal B6AF1 spleen cells, and rejection of the grafts by adoptively transferred sensitized cells was delayed (MST = 35 days). That the tolerance developed in response to grafting neonatal skin to ALS/BMC/CsA-treated recipients extends to adult tissue suggests that understanding of the immunoregulatory signal provided by the neonatal tissue might lead to a tolerogenic protocol for use with adult allografts.