Graft-specific tolerance after transplantation (B04)

• Subject Area: Gastroenterology
• Term: from 2007 to 2019
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 24899777

Project B04 explores the potential of using Foxp3+ regulatory T-cells for the induction of allospecific tolerance after organ transplantation. They showed in operational tolerant patients after liver transplantation that tolerance takes years to develop after cessation of all immunosuppressive drugs. They also demonstrated the major importance of local Treg accumulation within the graft in mouse and man. Finally, project B4 has demonstrated that antigen-specific Tregs are far more potent in tolerance induction as compared to polyspecific Tregs. B4 will now concentrate on two major aims. (1) Improving Treg therapy with classical nTregs. (2) The second focus will be on the generation of graft-specific Tregs, which recognize the graft via CARs. Thus, CAR-modified Tregs can be used to identify the graft independent of MHC restriction. In addition, CAR-modified Tregs could even be generated from nTregs years after transplantation, thereby enabling Treg-mediated weaning even long-term after transplantation.

• DFG Programme: Collaborative Research Centres
• Subproject of: SFB 738: Optimisation of Conventional and Innovative Transplants
• Applicant Institution: Medizinische Hochschule Hannover
• Project Head: Professor Dr. Elmar Jaeckel