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Induction of FOXP3-expressing regulatory CD4pos T cells by human mature autologous dendritic cells

✍ Scribed by Valérie Verhasselt; Olivier Vosters; Claire Beuneu; Charles Nicaise; Patrick Stordeur; Michel Goldman


Publisher
John Wiley and Sons
Year
2004
Tongue
English
Weight
351 KB
Volume
34
Category
Article
ISSN
0014-2980

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✦ Synopsis


Abstract

Current literature suggests that T cells recognizing antigen on mature dendritic cells (DC) differentiate into effector T cells whereas tolerance is induced when antigen is presented by immature DC. We investigated the consequences of the interactions between immature or lipopolysaccharide‐matured DC and CD4^pos^ T lymphocytes in absence of foreign antigen. While immature DC did not induce significant CD4^pos^ T cell activation, we observed that a significant fraction of CD4^pos^ T cells cultured with mature autologous DC displayed phenotypic features of activation and produced IL‐2, IFN‐γ, IL‐10 and TGF‐β. Furthermore, CD4^pos^ T lymphocytes primed by mature, but not immature, autologous DC acquired regulatory properties. Indeed, when added to an allogeneic mixed leukocyte reaction, they suppressed the response of alloreactive T lymphocytes to the priming DC while responses to third‐party stimulators were spared. The generation of CD4^pos^ T cells with regulatory function by autologous stimulation did not require the presence of natural CD4^pos^CD25^pos^ regulatory T cells. In addition, the acquisition ofregulatory function by CD4^pos^CD25^neg^ T cells stimulated by autologous mature DC was accompanied by the induction of FOXP3 expression. Our data suggest that during inflammatory conditions, presentation of self antigens by mature DC to autologous T lymphocytes could contribute to the generation of regulatory mechanisms.


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