MIGRATION OF LANGERHANS CELLS INTO HUMAN EPIDERMIS OF RECONSTRUCTED SKIN, NORMAL SKIN, OR HEALING SKIN, AFTER GRAFTING ONTO THE NUDE-MOUSE

Human skin equivalents composed of keratinocytes cultured on a lattice constituted of human fibroblasts embedded in type I collagen were gra fted onto the nude mouse. It is demonstrated, by indirect immunofluore scence and electron microscopy, that, after grafting, mouse Langerhans cells migrate into the human epidermis. Human Langerhans cells are no t present in this system. In split-thickness human skin grafts, at lon g periods (5 and 12 months) after transplantation, a progressive migra tion of murine Ia(+) cells in the human epidermis and the presence of human Langerhans cells were shown by indirect immunofluorescence. Crea tion of a wound at the center of the grafted human skin and identifica tion of the Langerhans cell origin shows a repopulation with human Lan gerhans cells provided the injury was performed early (2 months) after grafting. Injury at a later stage (5 months) resulted in presence of both human and murine Langerhans cells. These observations show 1) tha t, after grafting of ''reconstructed'' human skin or of split-thicknes s human skin onto nude mice, mouse Langerhans cells migrate into the g rafted human epidermis; and 2) that the Langerhans cells repopulating a healing grafted epidermis devoid of Langerhans cells derive from the non-injured surrounding epidermis. The present work thus shows that b esides bone marrow, lymph nodes, or/and spleen, surrounding cutaneous regions can also serve as sources of Langerhans cells.