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Inhibition of NF-kappa B and oxidative pathways in human dendritic cells by antioxidative vitamins generates regulatory T cells.

Publication ,  Journal Article
Tan, PH; Sagoo, P; Chan, C; Yates, JB; Campbell, J; Beutelspacher, SC; Foxwell, BMJ; Lombardi, G; George, AJT
Published in: J Immunol
June 15, 2005

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.

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Published In

J Immunol

DOI

ISSN

0022-1767

Publication Date

June 15, 2005

Volume

174

Issue

12

Start / End Page

7633 / 7644

Location

United States

Related Subject Headings

  • p38 Mitogen-Activated Protein Kinases
  • eIF-2 Kinase
  • alpha-Tocopherol
  • T-Lymphocytes, Regulatory
  • Signal Transduction
  • Reactive Oxygen Species
  • Protein Kinase C
  • Oxidation-Reduction
  • NF-kappa B
  • Intracellular Fluid
 

Citation

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Tan, P. H., Sagoo, P., Chan, C., Yates, J. B., Campbell, J., Beutelspacher, S. C., … George, A. J. T. (2005). Inhibition of NF-kappa B and oxidative pathways in human dendritic cells by antioxidative vitamins generates regulatory T cells. J Immunol, 174(12), 7633–7644. https://doi.org/10.4049/jimmunol.174.12.7633
Tan, Peng H., Pervinder Sagoo, Cliburn Chan, John B. Yates, Jamie Campbell, Sven C. Beutelspacher, Brian M. J. Foxwell, Giovanna Lombardi, and Andrew J. T. George. “Inhibition of NF-kappa B and oxidative pathways in human dendritic cells by antioxidative vitamins generates regulatory T cells.J Immunol 174, no. 12 (June 15, 2005): 7633–44. https://doi.org/10.4049/jimmunol.174.12.7633.
Tan PH, Sagoo P, Chan C, Yates JB, Campbell J, Beutelspacher SC, et al. Inhibition of NF-kappa B and oxidative pathways in human dendritic cells by antioxidative vitamins generates regulatory T cells. J Immunol. 2005 Jun 15;174(12):7633–44.
Tan, Peng H., et al. “Inhibition of NF-kappa B and oxidative pathways in human dendritic cells by antioxidative vitamins generates regulatory T cells.J Immunol, vol. 174, no. 12, June 2005, pp. 7633–44. Pubmed, doi:10.4049/jimmunol.174.12.7633.
Tan PH, Sagoo P, Chan C, Yates JB, Campbell J, Beutelspacher SC, Foxwell BMJ, Lombardi G, George AJT. Inhibition of NF-kappa B and oxidative pathways in human dendritic cells by antioxidative vitamins generates regulatory T cells. J Immunol. 2005 Jun 15;174(12):7633–7644.

Published In

J Immunol

DOI

ISSN

0022-1767

Publication Date

June 15, 2005

Volume

174

Issue

12

Start / End Page

7633 / 7644

Location

United States

Related Subject Headings

  • p38 Mitogen-Activated Protein Kinases
  • eIF-2 Kinase
  • alpha-Tocopherol
  • T-Lymphocytes, Regulatory
  • Signal Transduction
  • Reactive Oxygen Species
  • Protein Kinase C
  • Oxidation-Reduction
  • NF-kappa B
  • Intracellular Fluid