Skin allografts--lymph veiled (dendritic) cells are responsible for initiation of rejection in canine skin/SCID mouse chimera model.

Skin allografts are acutely rejected despite of intensive immunosuppressive therapy. Resistance of skin dendritic cells to immunosuppressive drugs and irradiation may be responsible for this phenomenon. Skin allograft is a site of interaction between the dendritic cells and lymphocytes of the donor and host origin and "direct" and "indirect" pathway of antigen presentation. Increasing evidence supports the significant role for the "indirect" allorecognition in graft rejection. To investigate a critical role of skin dendritic cells in the "indirect" allorecognition and graft destruction we have used a canine skin to severe-combined-immunodeficient (SCID)-mice transplantation model. At the time the skin grafts were deprived of own dendritic (Langerhans) cells, SCID mice were reconstituted with allogeneic canine whole lymph leukocytes, lymph lymphocytes, lymph veiled (dendritic) cells or peripheral blood mononuclear cells, and an early phase of skin rejection was evaluated in histopathological studies. We demonstrated that circulating canine allogeneic veiled cells facilitate recruitment of T lymphocytes into skin graft and promote an extensive graft destruction, compared to the less expressed effect of allogeneic peripheral lymph lymphocytes or blood mononuclear cells. These drug and radiation-resistant dendritic cells may be responsible for initiation of the difficult to control rejection process.