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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-kappaB) in human DCs inhibited the mixed leukocyte reaction. The aim of this study was to investigate the effect of blocking NF-kappaB 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 IotakappaBetaalpha, the endogenous inhibitor of NF-kappaB, led to a significant reduction in T-cell proliferation, and decreased production of interferon-gamma, IL-4 and IL-10, whereas transforming growth factor-beta 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-kappaB. The effective downregulation of antigen-specific T-cell responses following blockade of NF-kappaB in DCs could be a useful approach for immunomodulating inflammatory T-cell responses.

Original publication

DOI

10.1046/j.1365-3083.2003.01228.x

Type

Journal article

Journal

Scandinavian journal of immunology

Publication Date

03/2003

Volume

57

Pages

261 - 270

Addresses

Institute of Ophthalmology, UCL, London, UK. v.calder@ucl.ac.uk

Keywords

Dendritic Cells, T-Lymphocytes, Humans, NF-kappa B, Tetanus Toxoid, Epitopes, T-Lymphocyte, Lymphocyte Culture Test, Mixed, Flow Cytometry, Lymphocyte Activation, Signal Transduction, Cell Differentiation, Antigen Presentation, Immunologic Memory, Down-Regulation, I-kappa B Proteins