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  • Review Article
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CD4+CD25+FoxP3+ regulatory T cells in autoimmune diseases

Nature Clinical Practice Rheumatology volume 3, pages 619–626 (2007)Cite this article

Abstract

Maintenance of immune tolerance in the periphery can be envisioned as a balance between autoreactive lymphocytes and regulatory mechanisms that counteract them. The naturally occurring CD4+CD25+ regulatory T cells (TREGs) have a major role in modulating the activity of self-reactive cells. The identification of Forkhead box P3 transcription factor (FoxP3) as the critical determinant of TREG development and function has provided new opportunities and generated expanded interest in studying the balance between autoimmunity and regulatory mechanisms in human autoimmune diseases. The identification of both human and mouse diseases resulting from the lack of FoxP3 expression, and consequently the absence of TREGs, has rapidly expanded knowledge of TREG development and function during the past 5 years. Although it is still unclear how these regulatory cells function, they can inhibit the activation of potentially pathogenic T cells in vitro. Using in vitro functional assays and phenotypic analysis, TREGs isolated from patients with a variety of autoimmune diseases have been shown to exhibit reduced regulatory function as compared with those isolated from healthy controls. This Review will focus on the current state of knowledge on human TREGs and their association with specific autoimmune diseases.

Key Points

  • Regulatory T cells (TREGs) can be generated within the thymus or in peripheral tissues

  • Several autoimmune diseases have deficient TREG function during active disease

  • The proposed mechanisms of action of TREGs include influencing the migration of effectors to target organs or draining lymph nodes, prevention of priming by acting on antigen-presenting cells, induction of anergy in potential effectors, and prevention of the acquisition of effector function as effector T cells, killer effector cells or antigen-presenting cells

  • Studies investigating the function of TREGs in autoimmune diseases will provide further insight into the biology of these cells and might lead to the identification of new therapeutic targets

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Figure 1: Development of CD4+CD25hi regulatory T cells and their role in autoimmune diseases.

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Author information

Authors and Affiliations

  1. X Valencia is a physician scientist at the National Institute of Arthritis and Musculoskeletal and Skin Diseases, and PE Lipsky is the Head of the Autoimmunity Branch in the Intramural Research Program of the National Institute of Arthritis and Musculoskeletal and Skin Diseases, NIH, Bethesda, MD, USA. PE Lipsky is the Editor-in-Chief of Nature Clinical Practice Rheumatology.,

    Xavier Valencia & Peter E Lipsky

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  1. Xavier Valencia
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  2. Peter E Lipsky
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Correspondence to Xavier Valencia.

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The authors declare no competing financial interests.

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Valencia, X., Lipsky, P. CD4+CD25+FoxP3+ regulatory T cells in autoimmune diseases. Nat Rev Rheumatol 3, 619–626 (2007). https://doi.org/10.1038/ncprheum0624

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