Dendritic cells as regulators of immune reactivity: implications for skin transplantation

Skin allografts, in contrast to other organ transplants, are acutely rejected despite intensive and toxic for the graft recipient immunosuppressive therapy. Long-term immunosuppression increases the risk for life-threatening infections and cancers. This is why clinical skin allografting practically does not exist. Skin Langerhans' (dendritic) cells play a crucial role in the process of alloantigen recognition, its processing and initiation of the rejection reaction. These cells mature and migrate from the epidermis toward the dermal initial lymphatic vessels and further with afferent lymph, as veiled cells, they flow to the regional lymph nodes. Since a major goal in transplantation research is to understand and exploit the immunogenic properties of "passenger cells" as well as the tolerogenic properties of immature dendritic cells, studies concerning migrating less matured veiled cells obtained from afferent lymph draining skin seem to be relevant. Knowledge of mechanisms responsible for immunological synapse formation by veiled cells upon stimulation with allogeneic and bacterial antigens and of immunosuppressive drugs effect on this process, as well as of localization of Langerhans' cells in skin epidermis and dermis in the inflammatory foci, would facilitate a rational approach for the therapeutic protocols enabling the prolongation of skin allograft survival time.