Role of graft interleukin-10 expression in the tolerogenicity of neonatal skin allografts

Allografts of skin from neonatal donors survive longer than those from adult donors and can induce tolerance in mice that are treated with short-term immunosuppression. Neonatal (< or =24 hr old) epidermal cells (EPC) secrete high levels of interleukin-(IL) 10 and include abundant class II- immature Langerhans cells (LC). In this study, the role of IL-10 in the tolerogenicity of neonatal skin grafts was examined. After a preliminary experiment established that tolerogenesis by neonatal grafts could be supported by monoclonal antilymphocyte antibodies, B10.A(5R) recipients were immunosuppressed with anti-CD4 plus anti-CD8 (days 0, +2) and adult C57B1/6 bone marrow cells (day +7). Recipients were grafted with adult or neonatal C57B1/6 skin from wild-type or IL-10 deficient ("knockout" donors). EPC from wild-type and knockout neonatal skin were compared by flow cytometry, before and after 48 hr culture, to adult cells in terms of class II and costimulatory molecule expression. Grafts from knockout neonates survived longer than those from adult donors (median survival, MST=81 vs. 61 days), but not as long as those from wild-type neonates (MST=100 days; P