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Effective antigen presentation by dendritic cells is NF-kappaB dependent: coordinate regulation of MHC, co-stimulatory molecules and cytokines

Yoshimura, Satomichi, Bondeson, Jan, Foxwell, Brian M. J., Brennan, Fionula M. and Feldmann, Marc 2001. Effective antigen presentation by dendritic cells is NF-kappaB dependent: coordinate regulation of MHC, co-stimulatory molecules and cytokines. International Immunology 13 (5) , pp. 675-683. 10.1093/intimm/13.5.675

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Abstract

Antigen presentation is a key rate-limiting step in the immune response. Dendritic cells (DC) are the most potent antigen-presenting cells for naive T cells, due to their high expression of MHC and co-stimulatory molecules, but little is known about the biochemical pathways that regulate this function. We here demonstrate that monocyte-derived mature DC can be infected with adenovirus at high efficiency (>95%) and that this procedure can be used to dissect out which pathways are essential for inducing DC antigen presentation to naive T cells. Using adenoviral transfer of the endogenous inhibitor of NF-κB, IκBα, we show that DC antigen presentation is NF-κB dependent. The mechanism for this is that NF-κB is essential for three aspects of antigen-presenting function: blocking NF-κB coordinately down-regulates HLA class II, co-stimulatory molecules like CD80, CD86 and CD40, and immuno-stimulatory cytokines like IL-12 and tumor necrosis factor-α. In contrast adhesion molecules are up-regulated after infection with the adenovirus transferring IκBα, indicating that NF-κB also regulates the duration of T cell–DC interaction. These results establish NF-κB as an effective target for blocking DC antigen presentation and inhibiting T cell-dependent immune responses, and this finding has potential implications for the development of therapeutic agents for use in allergy, autoimmunity and transplantation.

Item Type: Article
Date Type: Publication
Status: Published
Schools: Medicine
Uncontrolled Keywords: adenovirus; antigen presentation; dendritic cell; NF-κB
Publisher: Oxford University Press
ISSN: 1460-2377
Last Modified: 30 Jun 2017 03:25
URI: http://orca-mwe.cf.ac.uk/id/eprint/57174

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