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

Leonie S Taams, Milica Vukmanovic-Stejic, Jay Smith, Padraic J Dunne, Jean M Fletcher, Fiona J Plunkett, Saskia B Ebeling, Giovanna Lombardi, Malcolm H Rustin, Johannes W J Bijlsma, Floris P J G Lafeber, Mike Salmon, Arne N Akbar

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218 Citations (Scopus)


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+CD45RBlow 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
Issue number6
Early online date21 May 2002
Publication statusPublished - 2002


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