PMID- 17335885
OWN - NLM
STAT- MEDLINE
DCOM- 20070706
LR  - 20131121
IS  - 0091-6749 (Print)
IS  - 0091-6749 (Linking)
VI  - 119
IP  - 5
DP  - 2007 May
TI  - Glutathione depletion inhibits dendritic cell maturation and delayed-type 
      hypersensitivity: implications for systemic disease and immunosenescence.
PG  - 1225-33
AB  - 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. CONCLUSION: Glutathione depletion downregulates T(H)1 immunity through a 
      perturbation of DC maturation and IL-12 production. CLINICAL IMPLICATIONS: These 
      data show that the induction of oxidative stress in the immune system, under 
      disease conditions and aging, interferes in T(H)1 immunity.
FAU - Kim, Hyon-Jeen
AU  - Kim HJ
AD  - Department of Medicine, Division of Clinical Immunology and Allergy, University 
      of California, Los Angeles, CA 90095, USA.
FAU - Barajas, Berenice
AU  - Barajas B
FAU - Chan, Ray Chun-Fai
AU  - Chan RC
FAU - Nel, Andre E
AU  - Nel AE
LA  - eng
GR  - R01 AG14992/AG/NIA NIH HHS/United States
GR  - U19 AI070453/AI/NIAID NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
DEP - 20070301
PL  - United States
TA  - J Allergy Clin Immunol
JT  - The Journal of allergy and clinical immunology
JID - 1275002
RN  - 0 (Reactive Oxygen Species)
RN  - 187348-17-0 (Interleukin-12)
RN  - 82115-62-6 (Interferon-gamma)
RN  - GAN16C9B8O (Glutathione)
SB  - IM
MH  - Adoptive Transfer
MH  - Animals
MH  - Cell Differentiation/immunology
MH  - Dendritic Cells/cytology/*immunology/metabolism
MH  - Enzyme-Linked Immunosorbent Assay
MH  - Female
MH  - Flow Cytometry
MH  - Glutathione/*antagonists & inhibitors/immunology
MH  - Hypersensitivity, Delayed/*immunology/metabolism
MH  - Interferon-gamma/metabolism
MH  - Interleukin-12/metabolism
MH  - Lymphocyte Activation/*immunology
MH  - Lymphocyte Culture Test, Mixed
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Oxidative Stress
MH  - Reactive Oxygen Species/antagonists & inhibitors/immunology
MH  - Reverse Transcriptase Polymerase Chain Reaction
MH  - Skin/cytology/immunology
MH  - Th1 Cells/immunology
EDAT- 2007/03/06 09:00
MHDA- 2007/07/07 09:00
CRDT- 2007/03/06 09:00
PHST- 2006/08/22 00:00 [received]
PHST- 2006/11/13 00:00 [revised]
PHST- 2007/01/05 00:00 [accepted]
PHST- 2007/03/06 09:00 [pubmed]
PHST- 2007/07/07 09:00 [medline]
PHST- 2007/03/06 09:00 [entrez]
AID - S0091-6749(07)00177-7 [pii]
AID - 10.1016/j.jaci.2007.01.016 [doi]
PST - ppublish
SO  - J Allergy Clin Immunol. 2007 May;119(5):1225-33. doi: 10.1016/j.jaci.2007.01.016. 
      Epub 2007 Mar 1.