title: Glutathione depletion inhibits dendritic cell maturation and delayed-type hypersensitivity: implications for systemic disease and immunosenescence.
abstract: BACKGROUND
  Dendritic cells (DCs) play a key role as antigen-presenting cells in the immune system. There is growing evidence that the redox equilibrium of these cells influences their ability to induce T-cell activation and to regulate the polarity of the immune response. This could affect the outcome of the immune response during systemic diseases and aging.
  
  
  OBJECTIVE
  Our aim was to elucidate the mechanism by which the redox equilibrium of antigen-presenting DCs affects the delayed-type hypersensitivity (DTH) response during experimental modification of glutathione levels, as well as during aging.
  
  
  METHODS
  We looked at the effect of glutathione depletion by diethyl maleate in DCs as well as during systemic administration on the DTH response to the contact-sensitizing antigens, oxazolone, and 2,4-dinitro-1-fluorobenzene. We also determined whether glutathione repletion with N-acetyl cysteine could influence the decline of the DTH response in aged mice.
  
  
  RESULTS
  Glutathione depletion in bone marrow-derived DCs interfered in their ability to mount a DTH response on adoptive transfer into recipient mice. Glutathione depletion interfered in IL-12 production and costimulatory receptor expression in DCs, leading to decreased IFN-gamma production in the skin of recipient mice. Systemic diethyl maleate treatment exerted similar effects on the DTH response and IFN-gamma production, whereas N-acetyl cysteine administration reversed the decline of the DTH response in aged animals.
  
  
  CONCLUSIONS
  Glutathione depletion downregulates T(H)1 immunity through a perturbation of DC maturation and IL-12 production.
  
  
  CONCLUSIONS
  These data show that the induction of oxidative stress in the immune system, under disease conditions and aging, interferes in T(H)1 immunity.
authors.affiliation: Department of Medicine, Division of Clinical Immunology and Allergy, University of California, Los Angeles, CA 90095, USA.
authors.forename: Hyon-Jeen
authors.initials: HJ
authors.lastname: Kim
authors.forename: Berenice
authors.initials: B
authors.lastname: Barajas
authors.forename: Ray Chun-Fai
authors.initials: RC
authors.lastname: Chan
authors.forename: Andre E
authors.initials: AE
authors.lastname: Nel
mesh_terms: D019264:Adoptive Transfer; D000818:Animals; D002454:Cell Differentiation / Q000276:immunology; D003713:Dendritic Cells / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005434:Flow Cytometry; D005978:Glutathione / Q000037:antagonists & inhibitors* / Q000276:immunology; D006968:Hypersensitivity, Delayed / Q000276:immunology* / Q000378:metabolism; D007371:Interferon-gamma / Q000378:metabolism; D018664:Interleukin-12 / Q000378:metabolism; D008213:Lymphocyte Activation / Q000276:immunology*; D007959:Lymphocyte Culture Test, Mixed; D051379:Mice; D008810:Mice, Inbred C57BL; D018384:Oxidative Stress; D017382:Reactive Oxygen Species / Q000037:antagonists & inhibitors / Q000276:immunology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012867:Skin / Q000166:cytology / Q000276:immunology; D018417:Th1 Cells / Q000276:immunology
chemical_list: D017382:Reactive Oxygen Species; D018664:Interleukin-12; D007371:Interferon-gamma; D005978:Glutathione