PMID- 15944264
OWN - NLM
STAT- MEDLINE
DCOM- 20050831
LR  - 20190516
IS  - 0022-1767 (Print)
IS  - 0022-1767 (Linking)
VI  - 174
IP  - 12
DP  - 2005 Jun 15
TI  - Inhibition of NF-kappa B and oxidative pathways in human dendritic cells by 
      antioxidative vitamins generates regulatory T cells.
PG  - 7633-44
AB  - Dendritic cells (DCs) are central to T cell immunity, and many strategies have 
      been used to manipulate DCs to modify immune responses. We investigated the 
      effects of antioxidants ascorbate (vitamin C) and alpha-tocopherol (vitamin E) on 
      DC phenotype and function. Vitamins C and E are both antioxidants, and concurrent 
      use results in a nonadditive activity. We have demonstrated that DC treated with 
      these antioxidants are resistant to phenotypic and functional changes following 
      stimulation with proinflammatory cytokines. Following treatment, the levels of 
      intracellular oxygen radical species were reduced, and the protein kinase 
      RNA-regulated, eukaryotic translation initiation factor 2alpha, NF-kappaB, 
      protein kinase C, and p38 MAPK pathways could not be activated following 
      inflammatory agent stimulation. We went on to show that allogeneic T cells 
      (including CD4(+)CD45RO, CD4(+)CD45RA, and CD4(+)CD25(-) subsets) were anergized 
      following exposure to vitamin-treated DCs, and secreted higher levels of Th2 
      cytokines and IL-10 than cells incubated with control DCs. These anergic T cells 
      act as regulatory T cells in a contact-dependent manner that is not dependent on 
      IL-4, IL-5, IL-10, IL-13, and TGF-beta. These data indicate that vitamin C- and 
      E-treated DC might be useful for the induction of tolerance to allo- or 
      autoantigens.
FAU - Tan, Peng H
AU  - Tan PH
AD  - Department of Immunology, Division of Medicine, Faculty of Medicine, Imperial 
      College London, Hammersmith Hospital, London, United Kingdom.
FAU - Sagoo, Pervinder
AU  - Sagoo P
FAU - Chan, Cliburn
AU  - Chan C
FAU - Yates, John B
AU  - Yates JB
FAU - Campbell, Jamie
AU  - Campbell J
FAU - Beutelspacher, Sven C
AU  - Beutelspacher SC
FAU - Foxwell, Brian M J
AU  - Foxwell BM
FAU - Lombardi, Giovanna
AU  - Lombardi G
FAU - George, Andrew J T
AU  - George AJ
LA  - eng
PT  - Comparative Study
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - J Immunol
JT  - Journal of immunology (Baltimore, Md. : 1950)
JID - 2985117R
RN  - 0 (Antioxidants)
RN  - 0 (Drug Combinations)
RN  - 0 (NF-kappa B)
RN  - 0 (Reactive Oxygen Species)
RN  - 7S5I7G3JQL (Dexamethasone)
RN  - EC 2.7.11.1 (eIF-2 Kinase)
RN  - EC 2.7.11.13 (Protein Kinase C)
RN  - EC 2.7.11.24 (p38 Mitogen-Activated Protein Kinases)
RN  - H4N855PNZ1 (alpha-Tocopherol)
RN  - PQ6CK8PD0R (Ascorbic Acid)
SB  - IM
MH  - Antioxidants/*pharmacology
MH  - Apoptosis/drug effects/immunology
MH  - Ascorbic Acid/*pharmacology
MH  - Cell Differentiation/immunology
MH  - Cells, Cultured
MH  - Clonal Anergy/drug effects/immunology
MH  - Dendritic Cells/drug effects/*immunology/*metabolism
MH  - Dexamethasone/pharmacology
MH  - Down-Regulation/drug effects/immunology
MH  - Drug Combinations
MH  - Humans
MH  - Immunophenotyping
MH  - Intracellular Fluid/immunology/metabolism
MH  - NF-kappa B/*antagonists & inhibitors/physiology
MH  - Oxidation-Reduction/drug effects
MH  - Protein Kinase C/antagonists & inhibitors/physiology
MH  - Reactive Oxygen Species/antagonists & inhibitors/metabolism
MH  - Signal Transduction/drug effects/*immunology
MH  - T-Lymphocytes, Regulatory/drug effects/*immunology/metabolism
MH  - alpha-Tocopherol/*pharmacology
MH  - eIF-2 Kinase/antagonists & inhibitors/physiology
MH  - p38 Mitogen-Activated Protein Kinases/antagonists & inhibitors/physiology
EDAT- 2005/06/10 09:00
MHDA- 2005/09/01 09:00
CRDT- 2005/06/10 09:00
PHST- 2005/06/10 09:00 [pubmed]
PHST- 2005/09/01 09:00 [medline]
PHST- 2005/06/10 09:00 [entrez]
AID - 174/12/7633 [pii]
AID - 10.4049/jimmunol.174.12.7633 [doi]
PST - ppublish
SO  - J Immunol. 2005 Jun 15;174(12):7633-44. doi: 10.4049/jimmunol.174.12.7633.