The biology and therapeutic potential of natural regulatory T-cells in the bone marrow transplant setting

Graft-versus-host disease (GVHD) remains a major barrier to the long-term success of allogeneic hematopoietic stem-cell transplantation for hematologic malignancies. This has prompted a great deal of interest in the development of alternative GVHD management strategies such as the adoptive transfer of lymphocytes with immunosuppressant activity. This review will focus on the biology of thymically derived regulatory T-cells (Tregs) and their potential therapeutic role in human bone marrow transplantation. A discussion of their basic suppressive mechanisms and invivo trafficking patterns will be presented, along with an overview of important preclinical studies using murine GVHD/tumor models. Currently available clinical data will also be discussed, including the contribution of Tregs to various transplant outcome parameters such as GVHD incidence and malignancy relapse rates.