Antigen-specific T cell suppression by human CD4(+)CD25(+) regulatory T cells

LS Taams, M Vukmanovic-Stejic, J Smith, PJ Dunne, JM Fletcher, FJ Plunkett, SB Ebeling, G Lombardi, MH Rustin, JWJ Bijlsma, FPJG Lafeber, Michael Salmon, AN Akbar

    Research output: Contribution to journalArticle

    214 Citations (Scopus)

    Abstract

    Anergic/suppressive CD4(+)CD25(+)T cells have been proposed to play an important role in the maintenance of peripheral tolerance. Here we demonstrate that in humans these cells suppress proliferation to self antigens, but also to dietary and foreign antigens. The suppressive CD4(+)CD25(+)T cells display a broad usage of the T cell receptor Vbeta repertoire, suggesting that they recognize a wide variety of antigens. They reside in the primed/memory CD4(+)CD45RO(+)CD45RB(low) subset and have short telomeres, indicating that these cells have the phenotype of highly differentiated CD4(+) T cells that have experienced repeated episodes of antigen-specific stimulation in vivo. This suggests that anergic/suppressive CD4(+)CD25(+)T cells may be generated in the periphery as a consequence of repeated antigenic encounter. This is supported by the observation that highly differentiated CD4(+)T cells can be induced to become anergic/suppressive when stimulated by antigen presented by non-professional antigen-presenting cells. We suggest that besides being generated in the thymus, CD4(+)CD25(+) regulatory T cells may also be generated in the periphery. This would provide a mechanism for the generation of regulatory cells that induce tolerance to a wide array of antigens that may not be encountered in the thymus.
    Original languageEnglish
    Pages (from-to)1621-1630
    Number of pages10
    JournalEuropean Journal of Immunology
    Volume32
    Issue number6
    DOIs
    Publication statusPublished - 1 Jun 2002

    Keywords

    • suppression
    • tolerance
    • anergy
    • telomere
    • immune regulation

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