Submitted July 7, 2006
Accepted November 2, 2006
Donor-derived cells and human graft-versus-host disease of the skin
Hideyuki Murata, Anne Janin, Christophe Leboeuf, Jean Soulier, Eliane Gluckman, Veronique Meignin, and Gerard P Socie*
INSERM U728, France
Universite Paris 7, U728, France
Hopital Saint-Louis, France
AP-HP, Hopital Saint-Louis, France
LRC CEA, France
* Corresponding author; email: gerard.socie{at}paris7.jussieu.fr.
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 HSCT recipients. Combining XY 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 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, while they were less numerous and found in the whole epidermis in late biopsies. Since donor derived cells were found at the site and at the time of maximum tissue damage, they could contribute to epidermal and micro-vessels repair.
