Stability of the Regulatory T Cell Lineage in Vivo
Self-Renewing T Cells
The homeostasis of cell populations within an organism can be achieved through a variety of mechanisms, including the differentiation of precursor populations, self-renewal of terminally differentiated cells, or by programming cells to be extremely long-lived. Regulatory T cells that express the transcription factor Foxp3 are critical for maintaining immune tolerance by preventing excessive inflammation and autoimmunity. Rubtsov et al. (p. 1667) now use genetic fate mapping and cell transfer studies in vivo to demonstrate that Foxp3-expressing cells are remarkably stable under both basal and inflammatory conditions. Thus, regulatory T cells appear to be maintained through self-renewal and should maintain their identity if used in adoptive cell therapies for treatment of autoimmunity or other inflammatory disorders.
Abstract
Tissue maintenance and homeostasis can be achieved through the replacement of dying cells by differentiating precursors or self-renewal of terminally differentiated cells or relies heavily on cellular longevity in poorly regenerating tissues. Regulatory T cells (Treg cells) represent an actively dividing cell population with critical function in suppression of lethal immune-mediated inflammation. The plasticity of Treg cells has been actively debated because it could factor importantly in protective immunity or autoimmunity. By using inducible labeling and tracking of Treg cell fate in vivo, or transfers of highly purified Treg cells, we have demonstrated notable stability of this cell population under physiologic and inflammatory conditions. Our results suggest that self-renewal of mature Treg cells serves as a major mechanism of maintenance of the Treg cell lineage in adult mice.
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Published In
Science
Volume 329 | Issue 5999
24 September 2010
24 September 2010
Copyright
Copyright © 2010, American Association for the Advancement of Science.
Submission history
Received: 7 May 2010
Accepted: 2 August 2010
Published in print: 24 September 2010
Acknowledgments
We thank K. Forbush, T. Chu, L. Karpik, A. Bravo, J. Herlihy, P. Zarin, G. Gerard, A. Ortiz-Lopes, and K. Hattori for assistance with mouse colony management; F. Costantini for R26Y mice; V. Kuchroo for Foxp3-IRES-GFP mice; P. Chambon for Cre-ERT2 plasmid; E. Pamer, C. Shi, and E. Leiner for L. monocytogenes and assistance with experiments; and P. Fink and K. Simmons for cells from Rag2pGFP mice and helpful discussion. R.E.N. was supported by NIH Medical Scientist Training Program grant GM07739. A.Y.R. is an investigator with the Howard Hughes Medical Institute, and this work was also supported by grant AI51530 from the NIH to C.B. and D.M.
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