Prolongation of adult skin allograft survival by cotransplantation of neonatal skin in antilymphocyte serum and donor bone marrow cell-treated mice.

Adult male B6AF1 (H-2KIb/kDb/d) mice were given skin allografts from adult male C3H (H-2k) mice, with and without contralateral cotransplants. The cotransplants were of either adult or neonatal (less than 24 hr) C3H skin. In recipient mice treated peritransplantation with antilymphocyte serum and posttransplantation with an i.v. injection of donor-strain bone marrow cells, the presence of a neonatal cotransplant resulted in significantly longer survival of the adult grafts. Median survival time (MST) for adult grafts, for the group that received a neonatal cotransplant was greater than 100 days, in comparison to MSTs of 59 days and 55 days for the groups that received only single adult grafts or the adult graft with an adult cotransplant. These results suggest an active immunomodulatory contribution of neonatal tissue, and we term this phenomenon the "cotransplant effect." This prolongation of survival of the adult grafts by the neonatal cotransplants was statistically significant in animals treated with ALS and BMC, but not in recipients that were treated with ALS only (MST = 34 days, in comparison with 29 days for groups that received either a single adult graft or an adult graft with an adult cotransplant). The graft-prolonging effects of an infusion of donor BMC thus appear to potentiate the expression of the cotransplant effect. An understanding of this effect may lead to improved methods of controlling the allograft response to adult tissues in the clinical setting.