Investigation into the Mechanisms of Transplantation Toleterance Induced by Peptide Vaccines

Naturally occurring CD4+CD25+ regulatory T (T-reg) cells not only play an important role in the maintenance of self-tolerance, but also control graft versus host disease and infectious disease, and prevent graft rejection. We have shown that the generation of adaptive CD4+ T-reg cells resulted from persistent but incomplete signaling in a mono-specific mouse and prevented allograft rejection. Antigen-reactive T-reg cells were also identified in the skin grafts. Female B6 mice are able to reject male B6 skin graft. In this project, we wish to further study the T cell regulation in this animal model. We wish to induce dominant transplantation tolerance to male skin graft with peptide-based vaccines in female B6 mice and to explore its underlying mechanism. Preliminary result showed that adoptive transfer of CD8+ T cell-depleted splenocytes could prevent male skin graft rejection by female mice. We will characterize the adaptive T-reg cells and study the extent of antigen specificity by testing linked suppression and infectious tolerance. To further understand the biology of the T-reg cells, we wish to explore the mode of action by the adaptive T-reg cells, including the interaction with dendritic cells, to demonstrate the distribution of T-reg cells and the role of IL-10 and IFN-γ in this peptide-induced tolerance. Finally, we study whether macrophage F4/80 receptor is required for the induction of antigen-specific CD4+ T-reg cells in this animal model. If we can realize the underlying mechanisms of transplantation tolerance, then we might be able to harness them for therapeutic benefit.

Project ID:PC9706-0163
External Project ID:NSC95-2320-B182-042-MY3