title: Proanthocyanidins inhibit UV-induced immunosuppression through IL-12-dependent stimulation of CD8+ effector T cells and inactivation of CD4+ T cells.
abstract: 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.
authors.affiliation: Department of Dermatology, University of Alabama at Birmingham, Birmingham, AL 35294, USA.
authors.forename: Mudit
authors.initials: M
authors.lastname: Vaid
authors.forename: Tripti
authors.initials: T
authors.lastname: Singh
authors.forename: Anna
authors.initials: A
authors.lastname: Li
authors.forename: Nandan
authors.initials: N
authors.lastname: Katiyar
authors.forename: Samriti
authors.initials: S
authors.lastname: Sharma
authors.forename: Craig A
authors.initials: CA
authors.lastname: Elmets
authors.forename: Hui
authors.initials: H
authors.lastname: Xu
authors.forename: Santosh K
authors.initials: SK
authors.lastname: Katiyar
mesh_terms: D019264:Adoptive Transfer; D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D003713:Dendritic Cells / Q000187:drug effects / Q000276:immunology / Q000528:radiation effects; D017453:Dermatitis, Irritant / Q000209:etiology / Q000276:immunology*; D019587:Dietary Supplements; D004139:Dinitrofluorobenzene / Q000494:pharmacology; D005260:Female; D056604:Grape Seed Extract / Q000008:administration & dosage / Q000494:pharmacology*; D007108:Immune Tolerance / Q000187:drug effects*; D053762:Interleukin-12 Subunit p40 / Q000502:physiology*; D008198:Lymph Nodes / Q000166:cytology; D008213:Lymphocyte Activation / Q000528:radiation effects; D051379:Mice; D008808:Mice, Inbred CBA; D018345:Mice, Knockout; D044945:Proanthocyanidins / Q000008:administration & dosage / Q000494:pharmacology*; D012867:Skin / Q000187:drug effects / Q000276:immunology / Q000528:radiation effects; D013154:Spleen / Q000166:cytology; D014466:Ultraviolet Rays; D027843:Vitis / Q000737:chemistry
chemical_list: D056604:Grape Seed Extract; C511402:Grape Seed Proanthocyanidins; D053762:Interleukin-12 Subunit p40; D044945:Proanthocyanidins; D004139:Dinitrofluorobenzene