| The identification of immunomodulatory approaches that allow the induction of antigen specific unresponsiveness is among the prerequisites for long-term graft survival without the complications of chronic immunosuppression. Peptide-based immunotherapy focuses on the induction of T cell tolerance either through modification of the stimulatory peptide (altered peptide ligands) or by delivering the stimulatory peptide to the immune system without the appropriate co-stimulatory signals. The succesful use of this approach in experimental auto-immune disease models prompts further studies on donor-specific T cell tolerance in transplantation. In this project, we aim to define conditions that will enable the arrest of the alloreactive response to processed allo-MHC, through direct interference in the CD4+ donor-specific T cell response, employing the principles of peptide-based therapy and/or interference in the co-stimulatory pathway. The ability of the tolerant T cell population to transfer that state to other donorspecific T cells previously not made tolerant will be an imporant issue in this study. |
