Department of Dermatology, University of Alabama at Birmingham, Birmingham, AL 35294, USA.
Cancer Prev Res (Phila). 2011 Feb;4(2):238-47. doi: 10.1158/1940-6207.CAPR-10-0224. Epub 2010 Nov 12.
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.
葡萄种子原花青素（GSP）通过饮食抑制 UVB 诱导的免疫抑制与在小鼠中诱导白细胞介素（IL）-12 有关，我们现在证实 GSP 不会抑制 IL-12p40 敲除（IL-12 KO）小鼠的 UVB 诱导的免疫抑制，并且用重组 IL-12 处理这些小鼠会恢复抑制作用。为了描述 GSP 介导的抑制 UVB 诱导的免疫抑制的细胞群体以及 IL-12 在该过程中的作用，我们使用了过继转移方法。从接受饮食 GSP（0.5％-1.0％，w / w）处理、暴露于 UVB 并通过在 UVB 暴露的皮肤上施用 2,4-二硝基氟苯（DNFB）致敏的小鼠中收获脾细胞和引流淋巴结。将 CD8（+）和 CD4（+）T 细胞进行阳性选择，并转移到随后在耳皮肤上施用 DNFB 接受挑战的幼稚小鼠中。从 GSP 处理、UVB 照射供体接受 CD8（+）T 细胞的幼稚受体表现出完全的接触超敏反应（CHS）反应。从 GSP 处理、UVB 暴露的小鼠接受 CD4（+）抑制性 T 细胞的幼稚小鼠在致敏和随后用 DNFB 挑战后可以引发 CHS 反应。在培养中，来自 GSP 处理、UVB 暴露的小鼠的 CD8（+）T 细胞分泌的 Th1 细胞因子水平（5-8 倍）高于未用 GSP 处理的 UVB 照射的小鼠的 CD8（+）T 细胞。来自 GSP 处理、UVB 暴露的小鼠的 CD4（+）T 细胞分泌的 Th2 细胞因子水平（80％-100％）明显低于未用 GSP 处理的 UVB 暴露的小鼠的 CD4（+）T 细胞。这些数据表明 GSP 通过刺激 CD8（+）效应 T 细胞和减少调节性 CD4（+）T 细胞来抑制 UVB 诱导的免疫抑制。
