title: Donor-derived cells and human graft-versus-host disease of the skin.
abstract: Graft-versus-host disease (GvHD)-induced apoptosis of the skin targets both epidermal keratinocytes and dermal endothelial cells. We studied the donor-versus-recipient origin of GvHD of these target cells in skin of 18 sex-mismatched hematopoietic stem-cell transplant (HSCT) recipients. Combining XY fluorescence in situ hybridization (FISH) and double immunostaining, and further 3D tissue Z-stack analysis, we found keratinocytes and endothelial cells of donor origin, but only in patients with GvHD. Using terminal dUTP nick-end labeling (TUNEL) assay on sister sections, we found a correlation between the numbers of chimeric and apoptotic epidermal and endothelial cells. Moreover, donor-derived cells were more numerous and preferentially distributed in the areas of severe GvHD damage in biopsies performed early in the course of GvHD, whereas they were less numerous and found in the whole epidermis in late biopsies. Because donor-derived cells were found at the site and at the time of maximum tissue damage, they could contribute to epidermal and microvessel repair.
authors.affiliation: Institut National de la Santé et de la Recherche Médicale (INSERM), U728, Paris, France.
authors.forename: Hideyuki
authors.initials: H
authors.lastname: Murata
authors.forename: Anne
authors.initials: A
authors.lastname: Janin
authors.forename: Christophe
authors.initials: C
authors.lastname: Leboeuf
authors.forename: Jean
authors.initials: J
authors.lastname: Soulier
authors.forename: Eliane
authors.initials: E
authors.lastname: Gluckman
authors.forename: Veronique
authors.initials: V
authors.lastname: Meignin
authors.forename: Gerard
authors.initials: G
authors.lastname: Socie
mesh_terms: D001706:Biopsy; D016026:Bone Marrow Transplantation / Q000009:adverse effects; D046528:Chimerism; D005260:Female; D006086:Graft vs Host Disease / Q000276:immunology* / Q000473:pathology*; D006801:Humans; D008297:Male; D012871:Skin Diseases / Q000276:immunology* / Q000473:pathology* / Q000601:surgery; D014019:Tissue Donors; D014184:Transplantation, Homologous