Control of T-cell activation by CD4+ CD25+ suppressor T cells

Authors

  • Ethan M. Shevach,

    Corresponding author
    1. Cellular Immunology Section, Laboratory of Immunology, National Institutes of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, USA
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  • Rebecca S. McHugh,

    1. Cellular Immunology Section, Laboratory of Immunology, National Institutes of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, USA
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  • Ciriaco A. Piccirillo,

    1. Cellular Immunology Section, 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. Cellular Immunology Section, Laboratory of Immunology, National Institutes of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, USA
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Correspondence to: Ethan M. Shevach
Laboratory of Immunology
National Institutes of Allergy and Infectious Diseases
National Institutes of Health
Building 10, Room 11N315
Bethesda MD 20892
USA
Fax: 1 301 496 0222
e-mail: ems1@mail.nih.gov

Abstract

Summary: Depletion of the minor (∼10%) subpopulation of CD4+ T cells that co-expresses CD25 (interleukin (IL)-2 receptor α-chain) by thymectomy of neonates on the third day of life or by treatment of adult CD4+ T cells with anti-CD25 and complement results in the development of organ-specific autoimmunity. Autoimmune disease can be prevented by reconstitution of the animals with CD4+ CD25+ cells. CD4+ CD25+-mediated protection of autoimmune gastritis does not require the suppressor cytokines IL-4, IL-10, or transforming growth factor (TGF)-β. Mice that express a transgenic T-cell receptor (TCR) derived from a thymectomized newborn that recognizes the gastric parietal cell antigen H/K ATPase all develop severe autoimmune gastritis very early in life. CD4+ CD25+ T cells are also powerful suppressors of the activation of both CD4+ and CD8+ T cells in vitro. Suppression is mediated by a cell contact-dependent, cytokine-independent T–T interaction. Activation of CD4+ CD25+ via their TCR generates suppressor effector cells that are capable of non-specifically suppressing the activation of any CD4+ or CD8+ T cell. Activation of suppressor effector function is independent of co-stimulation mediated by CD28/CTLA-4 interactions with CD80/CD86. We propose that CD4+ CD25+ T cells recognize organ-specific antigens, are recruited to sites of autoimmune damage where they are activated by their target antigen, and then physically interact with autoreactive CD4+ or CD8+ effector cells to suppress the development of autoimmune disease.

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