Tregs: application for solid-organ transplantation

Curr Opin Organ Transplant. 2012 Feb;17(1):34-41. doi: 10.1097/MOT.0b013e32834ee69f.

Abstract

Purpose of review: Transfer of human regulatory T cells (Tregs) has become an attractive therapeutic alternative to improve the long-term outcome in transplantation and thus reduce the side-effects of conventional immunosuppressive drugs. Here, we summarize the recent findings on human Treg subsets, their phenotype and in-vivo function.

Recent findings: In the last 2 years, it has become apparent that several Treg subsets exist that specifically regulate Th1-driven, Th2-driven, or Th17-driven immune responses; these subsets are very unstable and rapidly change their phenotype, for example, there is loss of Foxp3 expression upon extensive ex-vivo expansion and only the administration of rapamycin has been shown to be able to interfere reproducibly. New humanized mouse models incorporating human solid-organ grafts have been developed, which have been used to test the human Treg in-vivo function, and the first human Treg-cell products have been tested for safety and efficacy in stem cell transplantation.

Summary: With the recent findings, we have gained a better understanding of Treg heterogeneity, plasticity and function. Using the outcomes of clinical trials in stem cell transplantation, we have learned that adoptive therapy of Tregs is well tolerated and we are now awaiting the first result in solid-organ transplantation from the 'ONE Study'.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Disease Models, Animal
  • Forkhead Transcription Factors / drug effects
  • Forkhead Transcription Factors / immunology
  • Graft Rejection / immunology*
  • Graft Rejection / prevention & control*
  • Humans
  • Immunosuppression / methods*
  • Immunosuppressive Agents / therapeutic use
  • Immunotherapy, Adoptive / methods*
  • Organ Transplantation*
  • Sirolimus / therapeutic use
  • T-Lymphocytes, Regulatory / immunology*
  • T-Lymphocytes, Regulatory / physiology
  • Th1 Cells / immunology
  • Th17 Cells / immunology
  • Th2 Cells / immunology

Substances

  • FOXP3 protein, human
  • Forkhead Transcription Factors
  • Foxp3 protein, mouse
  • Immunosuppressive Agents
  • Sirolimus