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  • Review Article
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Mechanisms of Disease: the evolving role of regulatory T cells in atherosclerosis

Nature Clinical Practice Cardiovascular Medicine volume 5, pages 531–540 (2008)Cite this article

Abstract

Atherosclerosis and related complications still represent the major cause of morbidity and mortality in the western world. The mechanisms that govern the progression and destabilization of atheromatous lesions are multiple and complex. Despite their widespread use, lipid-lowering agents do not provide sufficient protection from future clinical cardiovascular-associated events. Interest in the role of immunity in atherosclerosis and support for this relationship has grown significantly over recent years. This paradigm, in which inflammation is an instrumental process in plaque development and rupture, is further supported by studies showing that immune subsets are operative in atherosclerosis. Regulatory T-cell subpopulations consist of lymphocytes—with several phenotypic markers—that share the ability to suppress, by various mechanisms, inflammatory responses. These regulatory T cells consist of subsets such as interleukin-10 secreting type I regulatory cells, type 3 effector T-helper cells that produce transforming growth factor-β, as well as adaptive and natural CD4+CD25+ regulatory T cells. In this Review, I focus on the direct and indirect evidence for the involvement of regulatory T cells in atherogenesis in experimental models and in humans. The growing knowledge of the role of regulatory T cells could result in the future development of novel therapeutic modalities to attenuate atherosclerosis and stabilize vulnerable plaques.

Key Points

  • The immune system has an active role in the initiation, progression and phenotype transition of the atherosclerotic plaque

  • Regulatory T cells comprise naturally occurring thymic-derived cells as well as adaptive antigen-triggered or interleukin-10 and transforming-growth-factor-β-producing cells

  • The major role of regulatory T cells is the downregulation of immune-mediated inflammation

  • The weight of evidence from studies employing transgenic atherosclerosis-prone mice suggests that regulatory T cells tune down experimental atherosclerosis

  • A more comprehensive understanding of the role of regulatory T cells in human atherosclerosis may shed light on mechanisms governing plaque destabilization and over a longer term perhaps aid the development of novel therapeutic modalities

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Figure 1: Mechanism(s) of immunosuppression by TREGs.
Figure 2: The potential involvement of regulatory T cells in atherosclerosis.

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Acknowledgements

Research in J George's laboratory is supported by a grant from the Israel Science Foundation No. 832/06. Charles P Vega, University of California, Irvine, CA, is the author of and is solely responsible for the content of the learning objectives, questions and answers of the Medscape-accredited continuing medical education activity associated with this article.

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  1. The Cardiovascular Research Center and the Department of Cardiology, Tel-Aviv Sourasky, Medical Center, 6 Weizmann Street, Tel-Aviv, Israel jacobg@post.tau.ac.il

Authors and Affiliations

  1. J George is Professor of Cardiology at the Department of Cardiology and the Cardiovascular Research Center, Tel Aviv Sourasky Medical Center and the Sackler Faculty of Medicine, Tel Aviv University, Israel.,

    Jacob George

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George, J. Mechanisms of Disease: the evolving role of regulatory T cells in atherosclerosis. Nat Rev Cardiol 5, 531–540 (2008). https://doi.org/10.1038/ncpcardio1279

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