The role of Langerhans cells in skin graft survival

This study investigated the role of donor class II major histocompatibility complex (MHC) glycoproteins, expressed on the plasma membrane of epidermal Langerhans cells (LC), in the initiation of murine skin allograft rejection. In normal skin LC are the only epidermal cell to express the class II MHC molecules. LC density was altered by topical application of a chemical carcinogen or exposure to short-wavelength ultraviolet light (UVB). The effects of these treatments were monitored by electron microscopic, irnrnunocytochemical and enzyme histochemical techniques, and correlated with skin graft survival. Skin was grafted onto hosts which differed genetically across the entire MHC region with minor transplantation differences, at the class I MHC region only, or at the class II MHC region only. Tolerance to the class II MHC glycoproteins developed in mice differing from the graft donor at the class II MHC region only. The mechanisms underlying the initiation and maintenance of tolerance were examined and the role of LC investigated. The effects of depleting class II MHC antigen from donor skin on the specificity of the cytotoxic T cell response which destroy histoincompatible grafts was examined in vitro and related to in vivo skin graft rejection. Skin allograft rejection remains a major clinical problem in the treatment of large surface area wounds. Therefore definition of the underlying mechanisms is important for the development of effective means of prolonging allograft survival.