| First Author | De Fazio SR | Year | 2000 |
| Journal | Transplantation | Volume | 70 |
| Issue | 9 | Pages | 1371-7 |
| PubMed ID | 11087155 | Mgi Jnum | J:65782 |
| Mgi Id | MGI:1927295 | Doi | 10.1097/00007890-200011150-00018 |
| Citation | De Fazio SR, et al. (2000) Role of graft interleukin-10 expression in the tolerogenicity of neonatal skin allografts. Transplantation 70(9):1371-7 |
| abstractText | BACKGROUND: 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. METHODS: 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. RESULTS: 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<0.05). As with normal neonatal EPC, neonatal knockout EPC expressed little class II antigen. Both types of neonatal EPC acquired class II in culture, and up-regulated CD80 and CD86 in an adult pattern, but failed to up-regulate class II antigen to the high level seen among cultured adult cells. CONCLUSIONS: The tolerogenicity of neonatal skin grafts derives in part from natural expression of IL-10 by the graft. Another possible contribution to tolerogenicity may be the inability of neonatal antigen presenting cells to up-regulate class II fully. Low expression of class II by neonatal cells is not attributable to epidermal IL-10 secretion. |
