Regulatory T cells in transplantation: what we know and what we do not know.

Current immunosuppressive regimens suppress alloimmunity by nonspecifically targeting T-cell proliferation, differentiation, and activation. In doing so, they have been effective in dramatically reducing rates of acute rejection and improving short-term allograft survival. However, this is often at the expense of overimmunosuppression. Furthermore, chronic rejection remains a significant problem. CD4(+)CD25(+)FoxP3(+) regulatory T cells (Treg) act to counterbalance effector mechanisms in immune homeostasis. Their function has been shown to be critical in autoimmune disease, transplantation, and allergy and inflammation. In this article, we will explore the current knowledge of Treg immunobiology in experimental models, as well as in human organ transplantation. The impact of current immunosuppressive agents on Tregs will be reviewed, and future promising targets for Treg-based therapies will be explored.