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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The transcription factor FOXP3 plays a key role in CD4 + CD25 + regulatory T cell function and represents a specific marker for these cells. Despite its strong association with regulatory T cell function, in humans little is known about the frequency of CD4 + CD25 + cells that express FOXP3 protein