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

Authors: Allan, Sarah E.¹; Broady, Raewyn¹; Gregori, Silvia²; Himmel, Megan E.¹; Locke, Natasha¹; Roncarolo, Maria Grazia; Bacchetta, Rosa²; Levings, Megan K.¹

Source: Immunological Reviews, Volume 223, Number 1, June 2008 , pp. 391-421(31)

Publisher: Wiley-Blackwell

Buy & download fulltext article:

Price: $48.00 plus tax (Refund Policy)

Abstract:

Summary

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.

Keywords: T-regulatory cells; cellular therapy; tolerance; Tr1 cells; FOXP3

Document Type: Research article

DOI: http://dx.doi.org/10.1111/j.1600-065X.2008.00634.x

Affiliations: 1: Department of Surgery, Immunity and Infection Research Centre, Vancouver Coastal Health Research Institute, University of British Columbia, Vancouver, BC, Canada. 2: San Raffaele Institute for Gene Therapy (HSR-TIGET), Milan, Italy.

Publication date: 2008-06-01