Document Detail

Proanthocyanidins inhibit UV-induced immunosuppression through IL-12-dependent stimulation of CD8+ effector T cells and inactivation of CD4+ T cells.
MedLine Citation:
PMID:  21075976     Owner:  NLM     Status:  MEDLINE    
The inhibition of UVB-induced immunosuppression by dietary grape seed proanthocyanidins (GSP) has been associated with the induction of interleukin (IL)-12 in mice, and we now confirm that GSPs do not inhibit UVB-induced immunosuppression in IL-12p40 knockout (IL-12 KO) mice and that treatment of these mice with recombinant IL-12 restores the inhibitory effect. To characterize the cell population responsible for the GSP-mediated inhibition of UVB-induced immunosuppression and the role of IL-12 in this process, we used an adoptive transfer approach. Splenocytes and draining lymph nodes were harvested from mice that had been administered dietary GSPs (0.5%-1.0%, w/w), exposed to UVB, and sensitized by the application of 2,4-dinitrofluorobenzene (DNFB) onto the UVB-exposed skin. CD8(+) and CD4(+) T cells were positively selected and transferred into naive mice that were subsequently challenged by application of DNFB on the ear skin. Naive recipients that received CD8(+) T cells from GSP-treated, UVB-irradiated donors exhibited full contact hypersensitivity (CHS) response. Naive mice that received CD4(+) suppressor T cells from GSP-treated, UVB-exposed mice could mount a CHS response after sensitization and subsequent challenge with DNFB. On culture, the CD8(+) T cells from GSP-treated, UVB-exposed mice secreted higher levels (5- to 8-fold) of Th1 cytokines than CD8(+) T cells from UVB-irradiated mice not treated with GSPs. CD4(+) T cells from GSP-treated, UVB-exposed mice secreted significantly lower levels (80%-100%) of Th2 cytokines than CD4(+) T cells from UVB-exposed mice not treated with GSPs. These data suggest that GSPs inhibit UVB-induced immunosuppression by stimulating CD8(+) effector T cells and diminishing regulatory CD4(+) T cells.
Mudit Vaid; Tripti Singh; Anna Li; Nandan Katiyar; Samriti Sharma; Craig A Elmets; Hui Xu; Santosh K Katiyar
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, U.S. Gov't, Non-P.H.S.     Date:  2010-11-12
Journal Detail:
Title:  Cancer prevention research (Philadelphia, Pa.)     Volume:  4     ISSN:  1940-6215     ISO Abbreviation:  Cancer Prev Res (Phila)     Publication Date:  2011 Feb 
Date Detail:
Created Date:  2011-02-04     Completed Date:  2011-05-19     Revised Date:  2013-07-03    
Medline Journal Info:
Nlm Unique ID:  101479409     Medline TA:  Cancer Prev Res (Phila)     Country:  United States    
Other Details:
Languages:  eng     Pagination:  238-47     Citation Subset:  IM    
Copyright Information:
©2010 AACR.
Department of Dermatology, University of Alabama at Birmingham, Birmingham, AL 35294, USA.
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MeSH Terms
Adoptive Transfer
CD4-Positive T-Lymphocytes / immunology*
CD8-Positive T-Lymphocytes / immunology*
Dendritic Cells / drug effects,  immunology,  radiation effects
Dermatitis, Irritant / etiology,  immunology*
Dietary Supplements
Dinitrofluorobenzene / pharmacology
Grape Seed Extract / administration & dosage,  pharmacology*
Immune Tolerance / drug effects*
Interleukin-12 Subunit p40 / physiology*
Lymph Nodes / cytology
Lymphocyte Activation / radiation effects
Mice, Inbred CBA
Mice, Knockout
Proanthocyanidins / administration & dosage,  pharmacology*
Skin / drug effects,  immunology,  radiation effects
Spleen / cytology
Ultraviolet Rays*
Vitis / chemistry
Grant Support
AR050948-01/AR/NIAMS NIH HHS; P30 AR050948/AR/NIAMS NIH HHS; P30 AR050948-01/AR/NIAMS NIH HHS; P30 AR050948-02/AR/NIAMS NIH HHS; P30 AR050948-03/AR/NIAMS NIH HHS; P30 AR050948-04/AR/NIAMS NIH HHS; P30 AR050948-05/AR/NIAMS NIH HHS; P30 AR050948-06/AR/NIAMS NIH HHS
Reg. No./Substance:
0/Grape Seed Extract; 0/Grape Seed Proanthocyanidins; 0/Interleukin-12 Subunit p40; 0/Proanthocyanidins; 70-34-8/Dinitrofluorobenzene

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