PMID- 12641655
OWN - NLM
STAT- MEDLINE
DCOM- 20030411
LR  - 20190818
IS  - 0300-9475 (Print)
IS  - 0300-9475 (Linking)
VI  - 57
IP  - 3
DP  - 2003 Mar
TI  - Antigen-specific T-cell downregulation by human dendritic cells following 
      blockade of NF-kappaB.
PG  - 261-70
AB  - Dendritic cells (DCs) are important for presenting antigen to T cells, especially 
      naive 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.
FAU - Calder, V L
AU  - Calder VL
AD  - Institute of Ophthalmology, UCL, London, UK. v.calder@ucl.ac.uk
FAU - Bondeson, J
AU  - Bondeson J
FAU - Brennan, F M
AU  - Brennan FM
FAU - Foxwell, B M J
AU  - Foxwell BM
FAU - Feldmann, M
AU  - Feldmann M
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - Scand J Immunol
JT  - Scandinavian journal of immunology
JID - 0323767
RN  - 0 (Epitopes, T-Lymphocyte)
RN  - 0 (I-kappa B Proteins)
RN  - 0 (NF-kappa B)
RN  - 0 (Tetanus Toxoid)
SB  - IM
MH  - Antigen Presentation/*immunology
MH  - Cell Differentiation
MH  - Dendritic Cells/cytology/*immunology
MH  - Down-Regulation
MH  - Epitopes, T-Lymphocyte/*immunology
MH  - Flow Cytometry
MH  - Humans
MH  - I-kappa B Proteins/pharmacology
MH  - Immunologic Memory/immunology
MH  - Lymphocyte Activation
MH  - Lymphocyte Culture Test, Mixed
MH  - NF-kappa B/*antagonists & inhibitors/immunology
MH  - Signal Transduction
MH  - T-Lymphocytes/*immunology
MH  - Tetanus Toxoid/immunology
EDAT- 2003/03/19 04:00
MHDA- 2003/04/12 05:00
CRDT- 2003/03/19 04:00
PHST- 2003/03/19 04:00 [pubmed]
PHST- 2003/04/12 05:00 [medline]
PHST- 2003/03/19 04:00 [entrez]
AID - 1228 [pii]
AID - 10.1046/j.1365-3083.2003.01228.x [doi]
PST - ppublish
SO  - Scand J Immunol. 2003 Mar;57(3):261-70. doi: 10.1046/j.1365-3083.2003.01228.x.