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Identification of a previously unknown antigen-specific regulatory T cell and its mechanism of suppression

Nature Medicine volume 6, pages 782–789 (2000)Cite this article

Abstract

Despite increasing evidence for the existence of antigen-specific regulatory T cells, the mechanisms underlying suppression remain unclear. In this study we have identified and cloned a novel subset of antigen-specific regulatory T cells and demonstrated that these T cells possess a unique combination of cell surface markers and array of cytokines. The regulatory T cells are able to inhibit the function of T cells carrying the same T-cell receptor specificity and prevent skin allograft rejection in an antigen-specific, dose-dependent manner. The regulatory T cells are able to acquire alloantigen from antigen-presenting cells, present the alloantigen to activated syngeneic CD8+ T cells and then send death signals to CD8+ T cells. These findings provide a novel mechanism of regulatory T-cell-mediated, antigen-specific suppression.

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Figure 1: DN T cells from the spleen of tolerant mice are able to inhibit anti-Ld responses in vivo and in vitro.
Figure 2: Dose-dependent inhibition of syngeneic CD8+ T cells in vitro by DN T cells.
Figure 3: a, DN regulatory T cells express a unique combination of cell surface markers and require direct cell contact for suppression.
Figure 4: DN T cells specifically lyse activated CD8+ T cells through the Fas/FasL pathway.
Figure 5: TCR -Ld interaction is critical for DN T-cell-mediated suppression.
Figure 6

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Acknowledgements

The authors thank P. Ohashi for providing LCMV-gp TCR transgenic mice and p33 peptides, H. Eilson for the 1B2 hybridoma, D.Y. Loh for providing a breeding stock of 2C transgenic mice and J. Chamberlain for providing HY Tg mice. The authors also thank J.M. Penninger, J. H. Russell, R.M. Gorczynski, R.G. Miller and M. Julius for critically reading the manuscript. This work is supported by Medical Research Council of Canada (MT 14431 to LZ) and Leukemia Research Fund of Canada (to L. Zhang).

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  1. Zhu-Xu Zhang and Liming Yang: contributed equally to this study.

Authors and Affiliations

  1. Department of Laboratory of Medicine and Pathobiology Multi Organ Transplantation Program, Toronto General Hospital Research Institute UHN, University of Toronto, M5G, 2C4, Toronto, Canada

    Zhu-Xu Zhang, Liming Yang, Kevin J. Young, Barb DuTemple & Li Zhang

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Correspondence to Li Zhang.

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Zhang, ZX., Yang, L., Young, K. et al. Identification of a previously unknown antigen-specific regulatory T cell and its mechanism of suppression. Nat Med 6, 782–789 (2000). https://doi.org/10.1038/77513

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