Modulation of xenogeneic responses via regulatory T cells

• Applicant: Professorin Dolores J. Schendel, Ph.D.
• Subject Area: Cardiac and Vascular Surgery
• Term: from 2010 to 2013
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 5470814

Within this research consortium, a number of different approaches are directed to the central goal of achieving long-term acceptance of xenogeneic transplants with preserved graft function, while avoiding chronic high-dose immunosuppressive drug regimens that are overtly detrimental to normal immune functions required for pathogen protection. Most strategies are directed to altering immune responses at the donor level through the development of multi-transgene pigs as the source of transplant organs or by modulating interactions of porcine antigen-presenting cells (APC) with donor responding cells to interfere with development of anti-donor responses. This project will explore strategies to minder T cell-mediated xenogeneic responses at the recipient level through the use of recipient-derived regulatory T cells. In the first phase, we will study the parameters for isolation and expansion of natural T regulatory cells (nTregs) from the baboon, as well as the generation of induced regulatory T cells (iTregs) using baboon dendritic cells that express porcinederived antigens. If suitable procedures can be found to generate adequate numbers of Tregs of stable phenotype with suppressive function ex vivo, then adoptive transfer studies will be carried out in the setting of pig to baboon heart transplantation to determine impact on graft function and survival in vivo.

• DFG Programme: Research Units
• Subproject of: FOR 535: Xenotransplantation
• Participating Person: Dr. Heike Pohla