Chirdo Fernando G, Millington Owain R, Beacock-Sharp Helen, Mowat Allan McI
Division of Immunology, Infection and Inflammation, Western Infirmary, Glasgow, Scotland.
Eur J Immunol. 2005 Jun;35(6):1831-40. doi: 10.1002/eji.200425882.
The lamina propria (LP) of the small intestine contains many dendritic cells (DC), which are likely to be in close contact with luminal antigens, but their role in intestinal immune responses has been overlooked. Here we show that after feeding mice ovalbumin (OVA), the majority of antigen uptake is associated with DC in the small intestinal LP, and we describe the isolation, purification and initial characterization of theses DC. We obtained >90% CD11c(+) DC using magnetic cell sorting, of which the majority were CD11b(+)CD8alpha(-), with smaller numbers of CD11b(-)CD8alpha(+) and CD11b(-)CD8alpha(-) DC as well as a distinct population of CD11c(int)class II MHC(lo) B220(+) DC. Freshly isolated LP DC expressed variable but generally low levels of CD40, CD80 and CD86, which were up-regulated by activation with LPS. LP DC were endocytic in vivo and in vitro and could present antigen to OVA-specific CD4(+) T cells in vitro. Antigen-loaded LP DC from OVA-fed mice also primed specific CD4(+) T cells in vivo and in vitro, but adoptive transfer of these DC into naive recipients induced hyporesponsiveness to subsequent challenge. LP DC also expressed significant levels of mRNA for IL-10 and type I IFN, but not IL-12, suggesting they may play a central and unique role in immune homeostasis in the gut.
小肠的固有层（LP）含有许多树突状细胞（DC），这些细胞可能与肠腔抗原密切接触，但其在肠道免疫反应中的作用一直被忽视。在此我们表明，给小鼠喂食卵清蛋白（OVA）后，大部分抗原摄取与小肠LP中的DC相关，并且我们描述了这些DC的分离、纯化及初步特性。我们通过磁珠细胞分选获得了>90%的CD11c(+) DC，其中大部分是CD11b(+)CD8α(-)，还有少量的CD11b(-)CD8α(+)和CD11b(-)CD8α(-) DC以及一群独特的CD11c(int)II类MHC(lo) B220(+) DC。新鲜分离的LP DC表达水平各异但总体较低的CD40、CD80和CD86，经脂多糖激活后这些分子上调。LP DC在体内和体外均具有内吞作用，并且在体外能够将抗原呈递给OVA特异性CD4(+) T细胞。来自喂食OVA小鼠的负载抗原的LP DC在体内和体外也能启动特异性CD4(+) T细胞，但将这些DC过继转移到未致敏的受体中会导致对后续攻击的低反应性。LP DC还表达显著水平的IL-10和I型干扰素的mRNA，但不表达IL-12，这表明它们可能在肠道免疫稳态中发挥核心且独特的作用。
