An in vivo model of human skin acute graft-versus-host disease: transplantation of cultured human epidermal cells and dermal fibroblasts with human lymphocytes into SCID mice

The ability of mixed epidermal cell-lymphocyte reactions to detect allogene ic reactivities in an in vivo model was investigated by developing an in vi vo model of acute graft-versus-host disease (GVHD), using SCID mice with a C.B-17 background in which human skin structures were generated by transpla ntation of cultured human epidermal cells (HEC) with dermal fibroblasts (HD FC), Suspensions containing cultured HEC and HDC from a single donor were m ixed with autologous peripheral blood mononuclear cells (PBMNC) or with PBM NC from unrelated individuals, and were injected into the flanks of C.B-17- SCID mice. Ten and 21 days after injection, subcutaneous nodules generated in the mice were examined histologically and immunohistochemically. Cystic structures developing after injection of HEC and HDFC without human PBMNC s howed normal epidermislike tissue. Human skin generated in SCID mice inject ed with HEC and HDFC with auto-PBMNC showed no graft-versus-host reaction ( GVHR) histologically, whereas those mice injected with PBMNC from siblings that shared an HLA haplotype showed mild GVHR, Human skin in SCID mice inje cted with HEC and HDFC with histoincompatible unrelated PBMNC showed modera te to severe GVHR, The severity of GVHR paralleled the dose of unrelated PB MNC, and GVHR was prevented by peroral treatment with cyclosporine A. Immun ohistochemically, inflammatory cells infiltrating human cutaneous tissue fo rmed in the SCID mice were stained by an anti-human CD45RO antibody that re acts with human T cells but not with murine lymphocytes, and most T cells w ere stained by an anti-human CD8 antibody recognizing HLA class I antigens, These findings are similar to those in clinical skin graft-versus host dis ease (GVHD) observed in patients undergoing allogeneic bone marrow transpla ntation. This experimental system should be useful as an in vivo model of h uman skin GVHD. (C) 1999 International Society for Experimental Hematology. Published by Elsevier Science Inc.