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The lifestyle of naturally occurring CD4+CD25+Foxp3+ regulatory T cells

Authors

  • Ethan M. Shevach,

    Corresponding author
    1. Laboratory of Immunology, National Institutes of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, USA.
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  • Richard A. DiPaolo,

    1. Laboratory of Immunology, National Institutes of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, USA.
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  • John Andersson,

    1. Laboratory of Immunology, National Institutes of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, USA.
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  • Dong-Mei Zhao,

    1. Laboratory of Immunology, National Institutes of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, USA.
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  • Geoffrey L. Stephens,

    1. Laboratory of Immunology, National Institutes of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, USA.
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  • Angela M. Thornton

    1. Laboratory of Immunology, National Institutes of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, USA.
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Ethan M. Shevach
Laboratory of Immunology
NIAID/NIH
Blg. 10, Room 11N315
Bethesda, MD 20892
USA
Tel.: +1 301 496 6449
Fax: +1 301 496 0222
E-mail: eshevach@niaid.nih.gov

Abstract

Summary:  Numerous studies over the past 10 years have demonstrated the importance of naturally occurring CD4+CD25+Foxp3+ regulatory T cells (nTregs) in immune regulation. We analyzed the mechanism of action of nTregs in a well-characterized model of autoimmune gastritis and demonstrated that nTregs act at an early stage of disease progression to inhibit the differentiation of naïve T cells to pathogenic T-helper 1 effectors. The effects of nTregs in this model are not antigen-specific but are mediated by activation of the nTregs by ubiquitous self-peptide major histocompatibility complex class II complexes together with cytokines released by activated effector cells. Studies in vitro confirmed that some nTregs exist in an activated state in vivo and can be activated to exert non-specific suppressor effector function by stimulation with interleukin-2 in the absence of engagement of their T-cell receptor. Natural Tregs can differentiate in vitro to exhibit potent granzyme B-dependent, partially perforin-independent cytotoxic cells that are capable of specifically killing antigen-presenting B cells. Natural Treg-mediated killing of antigen-presenting cells may represent one pathway by which they can induce long-lasting suppression of autoimmune disease.

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