Ethanol consumption modifies dendritic cell antigen presentation in mice
Ethanol consumption modifies dendritic cell antigen presentation in mice
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DOI：
10.1111/j.1530-0277.2007.00479.x
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发表时间：
2007-10-01
影响因子：
3.2
通讯作者：
Waltenbaugh, Carl
中科院分区：
文献类型：
--
作者：
Heinz, Richard;Waltenbaugh, Carl
饮酒在体内和体外都会损害1型细胞介导的适应性免疫反应。为探讨饮酒对BALB/c小鼠抗原提呈细胞(APC)数量和细胞因子产生的影响，对BALB/c小鼠分别饲喂含酒精、成对喂饲等热液对照和固体饲料11天。用顺势珠法分离巨噬细胞和树突状细胞(DC)，将卵蛋白(OVA)呈递给DO11.10 T细胞受体转基因小鼠来源的高纯度同基因CD4(+)T细胞。从饮食喂养的小鼠分离的DC也被用来向缺乏记忆T细胞的抗原未成熟的DO11.10Rag2(-/-)小鼠来源的高纯度CD4(+)T细胞提供OVA。采用双抗体夹心酶联免疫吸附试验检测细胞因子、IL-2、IL-6、IL-12、IL-13、IL-17A、干扰素-γ的水平。流式细胞仪检测了细胞表面分子的表达。饮酒削弱了迟发性超敏反应(类型1)，并提高了血清IgE水平(类型2)。CD11c(+)DC，而不是F4/80(+)巨噬细胞，支持纯化的CD4(+)T细胞的细胞因子反应。来自酒精消耗性BALB/c小鼠的CD11c(+)DC对DO11.10或DO11.10Rag2(-/-)小鼠来源的纯化的CD4(+)T细胞支持干扰素-γ反应的能力减弱。亚群分析表明，在小鼠脾中发现的3个“常规”DC亚群中，CD11c(+)CD8(α)(+)DC既负责OVA的呈递，也对乙醇的影响敏感。酒精摄入不会明显改变脾DC的百分比，但确实增加了这些细胞上CD11c的表面密度。数据显示，将纯化的CD4(+)T DO11.10细胞与来自饮酒小鼠的APC共培养后，OVA刺激可降低IL-6、IL-12、IL-17A和干扰素-γ，增加IL-13细胞因子的产生。乙醇改变CD11c(+)CD8(α)(+)DC功能，影响负责适应性免疫反应的细胞因子。对乙醇影响获得性免疫功能的基本机制(S)提出了统一的假说。
Alcohol consumption impairs type 1 cell-mediated adaptive immune responses both in vivo and in vitro. The present study investigated the effect of alcohol consumption on antigen-presenting cell (APC) populations and cytokine production.BALB/c were fed ethanol-containing, pair-fed isocaloric liquid control, or solid diets for 11 days. Macrophage and dendritic cell (DC) populations were isolated by paramagenetic bead separation and used to present ovalbumin (OVA) to highly purified syngeneic CD4(+) T cells derived from DO11.10 T cell receptor transgenic mice in coculture. DC isolated from diet-fed mice were also used to present OVA to highly purified CD4(+) T cells derived from antigen-naive DO11.10Rag2(-/-) mice that are devoid of memory T cells. In vitro cytokine responses, interleukin (IL) -2, IL-6, IL-12, IL-13, IL-17A, and interferon-gamma (IFN-gamma) were measured by enzyme-linked immunosorbent assay. Flow cytometry measured cell surface molecule expression.Alcohol consumption impairs delayed hypersensitivity responses (type 1) and enhances serum IgE levels (type 2). CD11c(+) DC, but not F4/80(+) macrophages, support cytokine responses by purified CD4(+) T cells. CD11c(+) DC derived from ethanol consuming BALB/c mice show diminished ability to support IFN-gamma responses by purified CD4(+) T cells derived from DO11.10 or DO11.10Rag2(-/-) mice. Subset analysis indicates that of the 3 "conventional" DC subsets found in mouse spleens, CD11c(+)CD8(alpha)(+) DCs are both responsible for OVA presentation and susceptible to the effects of ethanol. Ethanol consumption does not overtly alter the percent of splenic DC, but does increase the surface density of CD11c on these cells. Data show that cocultures containing purified CD4(+) T DO11.10 cells and APC derived from alcohol-consuming mice show decreased IL-6, IL-12, IL-17A, and IFN-gamma and increased IL-13 cytokine production in response to OVA stimulation.Ethanol alters CD11c(+)CD8(alpha)(+) DC function, affecting cytokines responsible for adaptive immune responses. A unifying hypothesis for the underlying mechanism(s) of ethanol's effect upon adaptive immune function is proposed.