Article abstract
Nature Immunology 10, 1000 - 1007 (2009)
Published online: 26 July 2009 | doi:10.1038/ni.1774
Instability of the transcription factor Foxp3 leads to the generation of pathogenic memory T cells in vivo
Xuyu Zhou1,4, Samantha L Bailey-Bucktrout1,4, Lukas T Jeker1,4, Cristina Penaranda1, Marc Martínez-Llordella3, Meredith Ashby1, Maki Nakayama2, Wendy Rosenthal1 & Jeffrey A Bluestone1
Abstract
Regulatory T cells (Treg cells) are central to the maintenance of immune homeostasis. However, little is known about the stability of Treg cells in vivo. In this study, we demonstrate that a substantial percentage of cells had transient or unstable expression of the transcription factor Foxp3. These 'exFoxp3' T cells had an activated-memory T cell phenotype and produced inflammatory cytokines. Moreover, exFoxp3 cell numbers were higher in inflamed tissues in autoimmune conditions. Adoptive transfer of autoreactive exFoxp3 cells led to the rapid onset of diabetes. Finally, analysis of the T cell receptor repertoire suggested that exFoxp3 cells developed from both natural and adaptive Treg cells. Thus, the generation of potentially autoreactive effector T cells as a consequence of Foxp3 instability has important implications for understanding autoimmune disease pathogenesis.
- Diabetes Center and the Department of Medicine, University of California, San Francisco, California, USA.
- Barbara Davis Center for Childhood Diabetes, University of Colorado Denver, Aurora, Colorado, USA.
- Present address: Liver Transplant Unit, Hospital Clínic Barcelona–August Pi Sunyer Institute for Biomedical Investigations, Barcelona, Spain.
- These authors contributed equally to this work.
Correspondence to: Jeffrey A Bluestone1 e-mail: jbluest@diabetes.ucsf.edu
