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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.

Original publication

DOI

10.1097/MOT.0b013e3283061137

Type

Journal article

Journal

Curr Opin Organ Transplant

Publication Date

08/2008

Volume

13

Pages

333 - 338

Keywords

Adoptive Transfer, Animals, Graft Rejection, Graft Survival, Humans, Immunosuppressive Agents, Organ Transplantation, T-Lymphocyte Subsets, T-Lymphocytes, Regulatory, Transplantation Tolerance, Transplantation, Homologous, Treatment Outcome