James W Verbsky1. 1. Department of Pediatrics, Division of Rheumatology, Medical College of Wisconsin, Milwaukee, Wisconsin 53201-1997, USA. jverbsky@mcw.edu
Abstract
PURPOSE OF REVIEW: The aim of this article is to review the potential use of T regulatory cells in pathologic immune responses, focusing on their clinical application and the challenges associated with these therapies. RECENT FINDINGS: Numerous T regulatory (TR) cell based therapies have been proposed to be clinically beneficial in patients with autoimmunity based on extensive studies in experimental models. Cell based therapies with CD4+CD25+Foxp3+ T regulatory cells isolated from peripheral blood hold promise, but difficulties exist in obtaining large enough numbers of these cells or expanding these cells in vitro. Generation of suppressive lymphocyte populations, such as cytokine secreting Tr1 and Th3 cells, is also promising. Therapies with Foxp3+ expressing lymphocytes generated from naïve CD4 lymphocytes in vitro is a novel mechanism of T regulatory cell generation, although questions regarding the role of these cells in vivo remain. Finally, therapies designed to restore the suppressive properties of T regulatory cells may be an alternative to cell-based therapies. SUMMARY: T regulatory cells hold considerable promise in the treatment of autoimmunity. There are many important questions, however, regarding the biology of these cells that need to be addressed before their broad implementation in human disease.
PURPOSE OF REVIEW: The aim of this article is to review the potential use of T regulatory cells in pathologic immune responses, focusing on their clinical application and the challenges associated with these therapies. RECENT FINDINGS: Numerous T regulatory (TR) cell based therapies have been proposed to be clinically beneficial in patients with autoimmunity based on extensive studies in experimental models. Cell based therapies with CD4+CD25+Foxp3+ T regulatory cells isolated from peripheral blood hold promise, but difficulties exist in obtaining large enough numbers of these cells or expanding these cells in vitro. Generation of suppressive lymphocyte populations, such as cytokine secreting Tr1 and Th3 cells, is also promising. Therapies with Foxp3+ expressing lymphocytes generated from naïve CD4 lymphocytes in vitro is a novel mechanism of T regulatory cell generation, although questions regarding the role of these cells in vivo remain. Finally, therapies designed to restore the suppressive properties of T regulatory cells may be an alternative to cell-based therapies. SUMMARY: T regulatory cells hold considerable promise in the treatment of autoimmunity. There are many important questions, however, regarding the biology of these cells that need to be addressed before their broad implementation in human disease.
Authors: Bruce Kirkham; Khaldoun Chaabo; Christopher Hall; Toby Garrood; Timothy Mant; Elizabeth Allen; Alexandra Vincent; Joana C Vasconcelos; Andrew T Prevost; Gabriel S Panayi; Valerie M Corrigall Journal: Rheumatology (Oxford) Date: 2016-08-07 Impact factor: 7.580
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