Antigen presentation by murine dendritic cells is nuclear factor-kappa B dependent both in vitro and in vivo

Yoshimura, S., Bondeson, Jan, Brennan, F. M., Foxwell, B. M. J. and Feldmann, M. 2003. Antigen presentation by murine dendritic cells is nuclear factor-kappa B dependent both in vitro and in vivo. Scandinavian Journal of Immunology 58 (2) , pp. 165-172. 10.1046/j.1365-3083.2003.01246.x

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Abstract

Antigen presentation is a key rate-limiting step in the immune response. Dendritic cells (DCs) have been reported to be the most potent antigen-presenting cells for naïve T cells, but little is known about the biochemical pathways that regulate this function. We here demonstrate that mature murine DC can be infected with adenovirus at high efficiency (>95%) and that an adenovirus transferring the endogenous inhibitor IκB blocks nuclear factor-kappa B (NF-κB) function in murine DC. This result indicates that antigen presentation in the mixed leucocyte reaction is NF-κB dependent, confirming data with human DC in vitro. However, the importance of this finding depends on verifying that this is true also in vivo. Using delayed type hypersensitivity with allogeneic cells, we show that NF-κB inhibition had a marked immunosuppressive effect in vivo. These results thus establish NF-κB as an effective target for blocking DC antigen presentation and hence inhibiting T-cell-dependent immune responses. This finding has potential implications for the development of therapeutic agents for use in various pathological conditions of the immune system, including allergy and autoimmunity, and also in transplantation.

Item Type:	Article
Date Type:	Publication
Status:	Published
Schools:	Medicine
Subjects:	R Medicine > R Medicine (General)
Publisher:	Wiley
ISSN:	03009475
Last Modified:	30 Jun 2017 03:25
URI:	https://orca.cardiff.ac.uk/id/eprint/57089

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