CD4+ T-regulatory cells: Toward therapy for human diseases

Sarah E. Allan, Raewyn Broady, Silvia Gregori, Megan E. Himmel, Natasha Locke, Maria Grazia Roncarolo, Rosa Bacchetta, Megan K. Levings

Research output: Contribution to journalArticle

Abstract

T-regulatory cells (Tregs) have a fundamental role in the establishment and maintenance of peripheral tolerance. There is now compelling evidence that deficits in the numbers and/or function of different types of Tregs can lead to autoimmunity, allergy, and graft rejection, whereas an over-abundance of Tregs can inhibit anti-tumor and anti-pathogen immunity. Experimental models in mice have demonstrated that manipulating the numbers and/or function of Tregs can decrease pathology in a wide range of contexts, including transplantation, autoimmunity, and cancer, and it is widely assumed that similar approaches will be possible in humans. Research into how Tregs can be manipulated therapeutically in humans is most advanced for two main types of CD4+ Tregs: forkhead box protein 3 (FOXP3)+ Tregs and interleukin-10-producing type 1 Tregs (Tr1 cells). The aim of this review is to highlight current information on the characteristics of human FOXP3+ Tregs and Tr1 cells that make them an attractive therapeutic target. We discuss the progress and limitations that must be overcome to develop methods to enhance Tregs in vivo, expand or induce them in vitro for adoptive transfer, and/or inhibit their function in vivo. Although many technical and theoretical challenges remain, the next decade will see the first clinical trials testing whether Treg-based therapies are effective in humans.

Original languageEnglish
Pages (from-to)391-421
Number of pages31
JournalImmunological Reviews
Volume223
Issue number1
DOIs
Publication statusPublished - Jun 2008

Keywords

  • Cellular therapy
  • FOXP3
  • T-regulatory cells
  • Tolerance
  • Tr1 cells

ASJC Scopus subject areas

  • Immunology

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    Allan, S. E., Broady, R., Gregori, S., Himmel, M. E., Locke, N., Roncarolo, M. G., Bacchetta, R., & Levings, M. K. (2008). CD4+ T-regulatory cells: Toward therapy for human diseases. Immunological Reviews, 223(1), 391-421. https://doi.org/10.1111/j.1600-065X.2008.00634.x