Tolerance For Skin Allograft Induced By FK506 And Bone Marrow Transplantation In A Model Of Severely Scalded Mice

[Background]After a large area and severe burn,on the one hand it is often difficult to close the wound by autologous skin graft at early stage since the serious lack of autologous skin source and the skin allograft transplantation can only cover the wound temporarily but not for long-term survival,which severely restricts the early treatment of major burn.Thus,how to induce donor-specific immune tolerance for the long-term survival or even permanent wound coverage of skin allograft has become a matter of concerned.On the other hand,the body shows severe immunosuppressive condition after major burn,especially the inhibition of T cell-mediated immunity,making the T cells appear hyporesponsiveness to allogeneic antigen,which is helpful for the successful implantation of allogeneic hematopoietic stem cells.That's to say,donor-specific immune tolerance can be induced by hematopoietic stem cell transplantation after low-intensity preconditioning,without myeloablative measures such as radiographic exposure all over the body,high-dose cytotoxic drugs or immunosuppressive agents.This study wanted to induce donor-specific immune tolerance and prolong the survival time of skin allograft through the formation of chimera induced by FK506 and bone marrow transplantation in a model of severely scalded mice.[Purpose]To investigate the feasibility of inducing specific tolerance for skin allograft in a model of severely scalded mice after preconditioned with high-dose of Tacrolimus(FK506) in a short period followed by bone marrow transplantation (BMT).[Contents]1.The establishment of the model of severely scalded mice and the observation of the change of T cell-mediated immunity after scald.2.Preconditioning of the scalded mice by FK506,bone marrow transplantation and skin grafting.3.Observation of the skin allograft survival,immunological rejection and the formation of chimera.[Results]1.After severe scald,the proportion of CD3~+ and CD4~+ T cells in the recipient mice decreased and the proportion of CD8~+ T cells increased.The ratio of CD4/CD8 significantly decreased,lower than normal value obviously.2.Short period of FK506 administration or bone marrow transplantation alone didn't led to prolonged survival time of skin allograft.3.The survival time of the skin allograft in the experimental group(FK506+ BMT) was 16.8±1.30 days,obviously longer than other groups(P＜0.05),and the recipient mice were still immunocompetent to the third part KM mice.4.The chimera rates in recipient's peripheral blood were 32%±2.7%,10%± 3.1%and 1.5%±0.2%at day 7,14,30 after scald respectively.[Conclusion]1.The T cell-mediated immunity was suppressed in severely scalded mice.2.Donor bone marrow transplantation after preconditioning by FK506 in severely scalded mice can promote the formation of mixed chimera.3.Specific immune tolerance of certain degree can be induced by mixed chimera in severely scalded mice and longer survival time of skin allograft was available.