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Regulatory T cells prevent catastrophic autoimmunity throughout the lifespan of mice

Nature Immunology volume 8, pages 191–197 (2007)Cite this article

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Abstract

Mice lacking the transcription factor Foxp3 (Foxp3−) lack regulatory T (Treg) cells and develop fatal autoimmune pathology. In Foxp3− mice, many activated effector T cells express self-reactive T cell receptors that are expressed in Treg cells in wild-type mice. Thus, in wild-type mice, most self-reactive thymocytes escaping negative selection are diverted into the Treg lineage, and whether Treg cells are critical in self-tolerance in wild-type mice remains unknown. Here, acute in vivo ablation of Treg cells demonstrated a vital function for Treg cells in neonatal and adult mice. We suggest that self-reactive T cells are continuously suppressed by Treg cells and that when suppression is relieved, self-reactive T cells become activated and facilitate accelerated maturation of dendritic cells.

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Figure 1: Characterization of inducible Treg cell ablation.
Figure 2: Consequences of chronic Treg cell elimination in neonates.
Figure 3: T cell activation in Foxp3− and Foxp3DTR mice depleted of Treg cells from birth.
Figure 4: Consequences of chronic Treg cell elimination in adult mice.
Figure 5: Kinetics of T cell activation in response to acute elimination of Treg cells from adult mice.
Figure 6: Increase in DC numbers after Treg cell elimination.

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Change history

  • 24 December 2006

    In the version of this article initially published online, a name in the first sentence of Acknowledgments is incorrect. The correct name is ‘M. Bevan’. The error has been corrected for all versions of the article.

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Acknowledgements

We thank D. Liggit for assistance with the analysis of histopathology; A. Gall, L. Karpik, T. Chu, K. Forbush, P. deRoos and M. Schwartz for assistance; R. Setoguchi and M. Bevan (University of Washington) for SMARTA Rag2−/− mice; and members of the Rudensky lab for discussions. The CD11c-DTR-GFP plasmid was a gift from R. Lang (Children's Hospital, Cincinnati, Ohio). Suported by the Howard Hughes Medical Institute (A.Y.R.), Cancer Research Institute (J.M.K.) and US National Institutes of Health (A.Y.R.).

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Authors and Affiliations

  1. Department of Immunology, University of Washington, Seattle, 98195, Washington, USA

    Jeong M Kim, Jeffrey P Rasmussen & Alexander Y Rudensky

  2. Howard Hughes Medical Institute, University of Washington, Seattle, 98195, Washington, USA

    Alexander Y Rudensky

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Correspondence to Alexander Y Rudensky.

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Supplementary information

Supplementary Fig. 1

Generation of the Foxp3DTR knockin allele. (PDF 827 kb)

Supplementary Fig. 2

Increased generation of myeloid dendritic cells in response to Treg cell elimination. (PDF 225 kb)

Supplementary Fig. 3

Increased expression of CD40L, RANKL, GM-CSF, IL-3 by CD4+ Foxp3− T cells after Treg cell elimination. (PDF 328 kb)

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Kim, J., Rasmussen, J. & Rudensky, A. Regulatory T cells prevent catastrophic autoimmunity throughout the lifespan of mice. Nat Immunol 8, 191–197 (2007). https://doi.org/10.1038/ni1428

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