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Regulatory T cells in experimental autoimmune disease

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Abstract

During the past 10 years, CD4+CD25+Foxp3+ regulatory T cells (Treg) have been extensively studied for their function in autoimmune disease. This review summarizes the evidence for a role of Treg in suppression of innate and adaptive immune responses in experimental models of autoimmunity including arthritis, colitis, diabetes, autoimmune encephalomyelitis, lupus, gastritis, oophoritis, prostatitis, and thyroiditis. Antigen-specific activation of Treg, but antigen-independent suppressive function, emerges as a common paradigm derived from several disease models. Treg suppress conventional T cells (Tcon) by direct cell contact in vitro. However, downmodulation of dendritic cell function and secretion of inhibitory cytokines such as IL-10 and TGF-β might underlie Treg function in vivo. The final outcome of autoimmunity vs tolerance depends on the balance between stimulatory signals (Toll-like receptor engagement, costimulation, and antigen dose) and inhibitory signals from Treg. Whereas most experimental settings analyze the capacity of Treg to prevent onset of autoimmune disease, more recent efforts indicate successful treatment of ongoing disease. Thus, Treg are on the verge of moving from experimental animal models into clinical applications in humans.

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Acknowledgements

We would like to thank all the researchers that have contributed to our knowledge about Treg in autoimmunity, and apologize to all of those we could not cite due to space constraints. We would like to thank P. Krammer, T. Trollmo, A. Cerwenka, J. Haas, V. Umansky, P. Beckhove, K. Hochweller, N. Oberle, N. Eberhardt, and I. Galani for critically reading the manuscript and helpful discussions.

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  1. Department of Neonatology, University of Heidelberg, Children’s Hospital, Im Neuenheimer Feld 180, 69120, Heidelberg, Germany

    Benedikt Fritzsching

  2. Division of Immunogenetics, D030, German Cancer Research Center, Im Neuenheimer Feld 280, 69120, Heidelberg, Germany

    Elisabeth Suri-Payer

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  1. Elisabeth Suri-Payer
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  2. Benedikt Fritzsching
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Correspondence to Elisabeth Suri-Payer.

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Suri-Payer, E., Fritzsching, B. Regulatory T cells in experimental autoimmune disease. Springer Semin Immun 28, 3–16 (2006). https://doi.org/10.1007/s00281-006-0021-8

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