Enhanced survival of skin grafts depleted of Langerhans' cells by treatment with dimethylbenzanthracene.
Langerhans' cells (LC) are the only subpopulation of epidermal cells to express the class II major histocompatibility (MHC) glycoproteins (H-2 Ia in the mouse) under normal conditions. Since these antigens are important in the initiation of allograft rejection, the effect of LC depletion on mouse skin graft survival was studied. Treatment with the chemical carcinogen 9, 10-dimethyl-1,2-benzanthracene (DMBA) was observed to deplete LC from the epidermis on ultrastructural examination. DMBA-treated C57BL dorsal trunk or tail skin grafted onto BALB/c recipients had a prolonged survival compared to solvent-treated donor skin. This was observed 1 week after a single DMBA treatment; successive once-weekly treatments or three treatments within 1 week failed to enhance allograft survival further. Tail-skin grafts had consistently longer survival times in comparison to dorsal trunk-skin grafts, for both control and treated skin. Treatment of dorsal trunk or tail skin with DMBA probably enhanced skin graft survival on allogeneic recipients by causing a loss of LC, and therefore of the class II MHC antigens from the graft. To confirm this, congenic mouse strains were used: B10.A(2R) x B10.A differing only at H-2D, and B10.A(2R) x B10.A(4R) differing only at H-2 I-E. Treatment of B10.A(2R) tail skin with DMBA for 1 week did not affect its survival when grafted onto H-2D-disparate B10.A mice, whereas when grafted onto H-2I-E-disparate B10.A(4R) hosts the DMBA-treated grafts were not only accepted permanently, but induced specific unresponsiveness. This confirms that the DMBA-induced enhancement of graft survival was the result of a loss of H-2 Ia antigens, and therefore of LC from the treated graft.
D015127:9,10-Dimethyl-1,2-benzanthracene; D000818:Animals; D006085:Graft Survival; D007801:Langerhans Cells / Q000187:drug effects / Q000648:ultrastructure*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D012867:Skin / Q000187:drug effects / Q000648:ultrastructure; D016038:Skin Transplantation
D015127:9,10-Dimethyl-1,2-benzanthracene