¹Department of Dermatology and Cutaneous Surgery, University of Miami Miller School of Medicine, Miami, Florida, USA

Without systemic immune suppression, allogeneic transplants are rejected via immunologic mechanisms (Kirsner et al., 1993) thought to involve delayed-type hypersensitivity reactions that are mediated by T cells. Foreign antigens (allograft antigens) are "presented" by antigen-presenting cells (APCs) as they activate T cells in lymph nodes and other secondary lymphoid tissue. Among the highly effective APCs are dendritic cells (DCs), which are thought to be essential to allogeneic graft recognition and rejection. At the time of transplantation, donor DCs are normally included in the transplanted organ or tissue (Lechler and Steinman, 2001). These cells have the capacity to migrate to regional lymph nodes where T-cell activation takes place. Specific to skin are the epidermal DCs, or Langerhans cells (LCs), which likewise are transferred from donor to host with allogeneic skin grafting. Donor LCs are also thought to be important in allogeneic skin graft rejection. The correlation of in vitro studies of LC function from mice to humans is complicated by the fact that LCs display differential effects depending on the environment in which they are studied.

Using a murine model lacking LCs, but retaining a full contingent of other DCs, Obhrai et al. (2008, this issue) tested the hypothesis that LCs are important in mediating allogeneic skin graft rejection. This is one of several mouse models that have previously been used to study LC function. Results from earlier work using this same animal model questioned the traditional role of LCs in delayed hypersensitivity reactions by finding, paradoxically, that contact sensitization is upregulated in the absence of LCs (Kaplan et al., 2005).

By performing genetic mismatched skin grafting experiments in various strains of mice and various types of mismatching using LC-deficient mice as donors, Obhrai et al. (2008) found that LCs were not required for skin graft rejection; grafts from LC-deficient mice were routinely rejected. This finding suggests that, at least in these mice, non-LC DCs probably play a role in skin graft rejection. More surprising was the finding that in a male–female mismatched experiment in which skin grafts are normally accepted (FVB mice), donor skin obtained from LC-deficient donors was rejected. This later finding suggests that LCs inhibit male antigen–associated skin graft rejection in certain strains of mice and warrants further investigation. The reason for this, and the mechanism by which it occurs, remain to be elucidated.

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