Alexandru Schiopu1, Kathryn J Wood. 1. Transplantation Research Immunology Group, Nuffield Department of Surgery, John Radcliffe Hospital, Oxford University, Headington, Oxford, United Kingdom.
Abstract
PURPOSE OF REVIEW: In recent years there has been increased interest in understanding the physiology and function of regulatory T cells. In this review we focus on the characterization of regulatory T-cell subsets and their potential therapeutic use in organ transplantation. RECENT FINDINGS: Regulatory T cells can play an instrumental role in the establishment of operational tolerance to allografts. The level of expression and the extent of posttranslational acetylation of the regulatory T-cell specific transcription factor Foxp3 are important modulators of their suppressive activity. Low expression of CD127 can be used as a novel marker to define pure regulatory T-cell populations and the expression of CD45RA on CD4CD25 regulatory T cells characterizes a population with a more stable phenotype upon expansion in vitro. Interleukin-35 is a recently discovered immunosuppressive cytokine secreted by CD4CD25 regulatory T cells. Although the presence of allospecific memory T cells in the pretransplant period and the use of immunosuppressants might interfere with the effectiveness of regulatory T-cell-based therapies, encouraging results indicate that the immunosuppressive drug rapamycin does not affect the expansion and function of regulatory T cells and could be included in a combined therapy. SUMMARY: Important advances have been made towards establishing regulatory T cells as a viable therapy in transplantation and the first clinical trials using human regulatory T cells are currently underway. There are, however, important limitations and safety issues that have to be addressed before this therapy can be fully translated into the clinic.
PURPOSE OF REVIEW: In recent years there has been increased interest in understanding the physiology and function of regulatory T cells. In this review we focus on the characterization of regulatory T-cell subsets and their potential therapeutic use in organ transplantation. RECENT FINDINGS: Regulatory T cells can play an instrumental role in the establishment of operational tolerance to allografts. The level of expression and the extent of posttranslational acetylation of the regulatory T-cell specific transcription factor Foxp3 are important modulators of their suppressive activity. Low expression of CD127 can be used as a novel marker to define pure regulatory T-cell populations and the expression of CD45RA on CD4CD25 regulatory T cells characterizes a population with a more stable phenotype upon expansion in vitro. Interleukin-35 is a recently discovered immunosuppressive cytokine secreted by CD4CD25 regulatory T cells. Although the presence of allospecific memory T cells in the pretransplant period and the use of immunosuppressants might interfere with the effectiveness of regulatory T-cell-based therapies, encouraging results indicate that the immunosuppressive drug rapamycin does not affect the expansion and function of regulatory T cells and could be included in a combined therapy. SUMMARY: Important advances have been made towards establishing regulatory T cells as a viable therapy in transplantation and the first clinical trials using human regulatory T cells are currently underway. There are, however, important limitations and safety issues that have to be addressed before this therapy can be fully translated into the clinic.
Authors: Giorgio Raimondi; Tina L Sumpter; Benjamin M Matta; Mahesh Pillai; Natasha Corbitt; Yoram Vodovotz; Zhiliang Wang; Angus W Thomson Journal: J Immunol Date: 2009-12-09 Impact factor: 5.422