Antigen-specific T-Cell downregulation by human dendritic cells following blockade of NF-kappaB

Calder, V. L., Bondeson, Jan, Brennan, F. M., Foxwell, B. M. J. and Feldmann, M. 2003. Antigen-specific T-Cell downregulation by human dendritic cells following blockade of NF-kappaB. Scandinavian Journal of Immunology 57 (3) , pp. 261-270. 10.1046/j.1365-3083.2003.01228.x

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Abstract

Dendritic cells (DCs) are important for presenting antigen to T cells, especially naïve T cells. It has recently been shown that blocking the transcription factor, nuclear factor kappa B (NF-κB) in human DCs inhibited the mixed leukocyte reaction. The aim of this study was to investigate the effect of blocking NF-κB in DCs during presentation of antigen to memory T cells in vitro. Peripheral blood monocytes were differentiated into immature DCs with interleukin-4 (IL-4) and granulocyte-macrophage colony-stimulating factor, and pulsed with an immunogenic tetanus toxoid peptide. Upon maturation, the antigen-pulsed DCs were highly effective in presenting antigen to autologous T cells. However, stimulation with antigen-pulsed DCs overexpressing ΙκΒ, the endogenous inhibitor of NF-κB, led to a significant reduction in T-cell proliferation, and decreased production of interferon-, IL-4 and IL-10, whereas transforming growth factor-β production was low throughout. There was a significant increase in apoptosis of antigen-specific T cells, even in the presence of IL-2, which was not found in resting T cells. Similar findings were observed using a proteasome inhibitor to block NF-κB. The effective downregulation of antigen-specific T-cell responses following blockade of NF-κB in DCs could be a useful approach for immunomodulating inflammatory T-cell responses.

Item Type:	Article
Date Type:	Publication
Status:	Published
Schools:	Medicine
Subjects:	R Medicine > R Medicine (General)
ISSN:	03009475
Last Modified:	30 Jun 2017 03:25
URI:	https://orca.cardiff.ac.uk/id/eprint/57094

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