Antigen-specific T cell suppression by human CD4+CD25+ regulatory T cells.
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.
Taams
Leonie S
LS
Department of Rheumatology and Clinical Immunology, University Medical Center Utrecht, Utrecht, The Netherlands. L.S.Taams@azu.nl
Vukmanovic-Stejic
Milica
M
Smith
Jay
J
Dunne
Padraic J
PJ
Fletcher
Jean M
JM
Plunkett
Fiona J
FJ
Ebeling
Saskia B
SB
Lombardi
Giovanna
G
Rustin
Malcolm H
MH
Bijlsma
Johannes W J
JW
Lafeber
Floris P J G
FP
Salmon
Mike
M
Akbar
Arne N
AN
D000941:Antigens / Q000276:immunology*; D015704:CD4 Antigens / Q000032:analysis*; D002454:Cell Differentiation; D019674:Genes, T-Cell Receptor beta; D006801:Humans; D007108:Immune Tolerance; D015375:Receptors, Interleukin-2 / Q000032:analysis*; D013601:T-Lymphocytes / Q000276:immunology*; D016615:Telomere
D000941:Antigens; D015704:CD4 Antigens; D015375:Receptors, Interleukin-2