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Regulatory T-cell physiology and application to treat autoimmunity

Qizhi Tang
Jeffrey A. Bluestone

Authors

  • Qizhi Tang,

    1. UCSF Diabetes Center, Department of Medicine and Department of Pathology, University of California, San Francisco, CA, USA
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  • Jeffrey A. Bluestone

    Corresponding author
    1. UCSF Diabetes Center, Department of Medicine and Department of Pathology, University of California, San Francisco, CA, USA
      Jeffrey A. Bluestone
      UCSF Diabetes Center
      HSW 1118, Box 0540
      513 Parnassus Avenue
      San Francisco, CA 94143-0540
      USA
      Tel.: +1 415 514 1683
      Fax: +1 415 564 5813
      E-mail: jbluest@diabetes.ucsf.edu
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Jeffrey A. Bluestone
UCSF Diabetes Center
HSW 1118, Box 0540
513 Parnassus Avenue
San Francisco, CA 94143-0540
USA
Tel.: +1 415 514 1683
Fax: +1 415 564 5813
E-mail: jbluest@diabetes.ucsf.edu

Abstract

Summary:  Endowed with the ability to actively suppress an immune response, regulatory T cells (Tregs) hold the promise of halting ongoing pathogenic autoimmunity and restoring self-tolerance in patients suffering from autoimmune diseases. Through many in vitro and in vivo studies, we have learned that Tregs can function in the lymph nodes as well as in the peripheral tissues. In vivo, Tregs act through dendritic cells to limit autoreactive T-cell activation, thus preventing their differentiation and acquisition of effector functions. By limiting the supply of activated pathogenic cells, Tregs prevent or slow down the progression of autoimmune diseases. However, this protective mechanism appears insufficient in autoimmune individuals, likely because of a shortage of Tregs cells and/or the development and accumulation of Treg-resistant pathogenic T cells over the long disease course. Thus, restoration of self-tolerance in these patients will likely require purging of pathogenic T cells along with infusion of Tregs with increased ability to control ongoing tissue injury. In this review, we highlight advances in dissecting Treg function in vivo in autoimmune settings and summarize multiple studies that have overcome the limitations of the low abundance of Tregs and their hypoproliferative phenotype to develop Treg-based therapies.

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