Graft-versus-host disease (GvHD) remains a major complication after allogeneic hematopoietic stem-cell-transplantation. Present GvHD prophylaxis and treatment is still based on unspecific immunosuppressive drug therapy. Over the last decade, the potential of cell-based therapies involving the infusion of regulatory T cells has emerged as a feasible alternative approach for the treatment and prevention of GvHD. Here we review current efforts to translate data obtained in rodent models into clinical trials. Special emphasis is placed on the variety of strategies to generate sufficient numbers of alloantigen-specific regulatory T cells for adoptive cell therapy. This can be achieved either by expansion or by induction of a regulatory phenotype in naive T cells. Stability of the immunosuppressive phenotype of transferred regulatory T cells even in the highly inflammatory environment of acute GvHD will be thereby a critical parameter for actual therapeutic application.
