Abstract
Abstract The immunosuppressive effects of solar ultraviolet (UV) radiation, particularly UVB (290-320 nm), are well recognized. Experimental evidence indicates that UV-induced immunosuppression is a risk factor for skin cancer development, including melanoma and non-melanoma, in mice and clinical evidence suggests that it is also a risk factor in humans. Conversely, animals with an enhanced immune response exhibit a lower risk of skin tumor development on chronic UV exposure. Dietary grape seed proanthocyanidins (GSPs) have been shown to inhibit UVB-induced immunosuppression in mice; however, the cellular and molecular mechanisms underlying this inhibitory effect of GSPs are not yet clearly understood. To characterize the cell population responsible for the GSPs-mediated inhibition of UVB-induced immunosuppression, we used an adoptive transfer approach. Splenocytes and draining lymph nodes were harvested from mice that had been administered dietary GSPs, exposed to UVB, and sensitized by topical application of 2,4-dinitorfluorobenzene (DNFB) onto the UVB-exposed skin. CD8+ and CD4+ T cells were positively selected and transferred into naïve mice that were subsequently challenged by application of DNFB on the ear skin. Naïve recipients that received CD8+ T cells from GSPs-treated, UVB-irradiated donors exhibited full contact hypersensitivity (CHS) response. CHS is considered to be a prototypic T-cell mediated immune response. Naïve mice that received CD4+ regulatory T cells from GSPs-treated, UVB-exposed mice were able to mount a CHS response after sensitization and subsequent challenge with DNFB. On culture, the CD8+ T cells from GSPs-treated, UVB-exposed mice secreted higher levels of Th1 cytokines (IL-2, IFNγ) than CD8+ T cells from UVB-irradiated mice not treated with GSPs. CD4+ T cells from GSPs-treated, UVB-exposed mice secreted significantly lower levels of Th2 cytokines (IL-4 and IL-10) than CD4+ T cells from UVB-exposed mice not treated with GSPs. These data suggest that dietary GSPs inhibit UVB-induced immunosuppression by stimulating CD8+ effector T cells and diminishing regulatory CD4+ T cells in mice. This property of GSPs can be used as an alternative strategy to augment the induction of CD8+ effector T cells and to diminish the development of CD4+ regulatory T cells and that may lead to the prevention of skin cancer risk in humans. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 810. doi:10.1158/1538-7445.AM2011-810
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