The Induction Of Skin Transplantation Tolerance In Mice By Third-Party Dendritic Cells Loaded With Donor's Antigens

With a number of developments in burn research and care, a patient with full-thickness large body burns can overcome the hurt of shock and early-stage failure of organs. However, a new obstacle becomes conspicuous, that is how to cover the extensive wound bed with limited autogeneic skin. Burn mortality is largely due to end-stage failure of a critically important organ-skin which is followed by the multiple manifestations, including fluid loss, metabolic problems, immunodeviations, and most critically sepsis. As a result, it has become the"bottle-neck"of the treatment in severe burn patients.Recent studies in organ transplantation have implicated that allogeneic skin transplantation maybe a promising way in the treatment of massive skin defects. But skin grafts could only survival for a short time because of host versus graft reaction. Although immunosuppressive drugs could be efficacious for preventing the grafts from the attack of host's immune system, they can cause severe infection, which are not suitable for all patients. Therefore how to establish antigen (Ag)-specific tolerance has been a long sought-after goal. Ag-specific tolerance is a technique to induce a nonreactive state in a recipient to a given limited number of Ags expressed by the donor while permitting the retention of full immunocompetence toward the extraordinary number of foreign Ags in the environment. Many experimental data have confirmed that infusion of donor-derived immature dendritic cells (DCs) can improve allograft survival in rodent animal models. Binding of membrane T cell receptor on naive T lymphocytes to MHC-bound peptide molecules expressed on the surface of donor-drived immature DCs (signal 1) in the absence (or low levels) of T cell costimulation (signal 2) leads to anergy or apoptosis of the Ag- specific T cells. Be based on these results, immature DCs or gene modified DCs have been the focus in recent studies, and have clear advantages in kidney, liver, heart, pancreatic islet and small intestine transplantation.However, the origen of DCs is always not the same with that of skin in clinic, which...