Role of regulatory T cells in the promotion of transplant tolerance

Liver transplantation is now recognized as the most effective therapy for patients with end‐stage acute and chronic liver failure. Despite outstanding short‐term graft and patient survival, liver transplantation continues to face several major challenges, including poor long‐term graft survival due to chronic rejection and major side effects of long‐term immunosuppressive therapy (which is required for the prevention of rejection). The ability to produce a state of tolerance after transplantation would potentially obviate long‐term immunosuppression. Self‐tolerance and immune homeostasis involve both central and peripheral immunoregulatory mechanisms. To date, studies have shown that many subsets of regulatory T cells (Tregs) control immune responses to foreign and alloantigens. The identification of Tregs that are positive for CD4, CD25, and the transcription factor forkhead box (Foxp3) has resulted in major advances in our understanding of the immunology of rejection and the development of transplant tolerance. In this article, we focus on the importance of Tregs in tolerance induction in experimental models of liver transplantation. Furthermore, we discuss the therapeutic potential of Tregs for the promotion of tolerance in transplant patients and highlight recent clinical trials of Treg‐based therapies. Liver Transpl, 2012. © 2012 AASLD.