Ruedl C, Rieser C, Böck G, Wick G, Wolf H
Institute for General and Experimental Pathology, Medical School, University of Innsbruck, Austria.
Eur J Immunol. 1996 Aug;26(8):1801-6. doi: 10.1002/eji.1830260821.
The antigen-presenting cell system in the gastrointestinal tract, one of three main sites (skin and lung being the others) of primary antigen contact, is poorly understood. Our study focused on dendritic cells (DC) as possible candidates for antigen uptake, processing and presentation in mucosal inductive sites, such as Peyer's patches (PP). To investigate the morphology, immunophenotype and stimulatory activity of intestinal DC, a procedure was developed to obtain a cell population by using collagenase digestion of PP, density centrifugation and cell sorting on the basis of CD11c expression. The resultant low-density cell fraction consisted of a nonadherent cell population expressing different intensities of CD11c that could at least be characterized by typical DC morphology (e.g. abundant cytoplasma with veil-like cytoplasmatic dendrites, irregularly shaped nuclei, multivesicular and multilamellar bodies), constitutive levels of surface MHC class II, the presence of macrophage-specific markers, such as F4/80, Mac-I and Fc receptors, respectively, on subpopulations of CD11c+ sorted cells and expression of adhesion and co-stimulatory receptors like ICAM-1 and CD44. The capability of this low-density CD11c+ fraction to stimulate T cell responses was demonstrated in primary allogeneic mixed-lymphocyte reactions (MLR). Herein, we show that the freshly isolated CD11c+ cells showed weak accessory function, but develop this capacity following short-term culture in vitro in the presence of granulocyte/macrophage colony-stimulating factor. Although the nature and functional capacity of the isolated CD11c+ needs further clarification, these preliminary results describing phenotype and accessory function provide some evidence that these cells isolated from the PP may be immature forms of DC and play a crucial role as antigen-presenting cells with important implications for understanding the complex network regulating intestinal antigen uptake, processing and presentation.
胃肠道中的抗原呈递细胞系统是初次抗原接触的三个主要部位之一（其他两个部位是皮肤和肺），目前人们对其了解甚少。我们的研究聚焦于树突状细胞（DC），它可能是黏膜诱导部位（如派尔集合淋巴结，PP）中摄取、处理和呈递抗原的候选细胞。为了研究肠道DC的形态、免疫表型和刺激活性，我们开发了一种程序，通过用胶原酶消化PP、密度离心以及基于CD11c表达进行细胞分选来获得细胞群体。所得的低密度细胞组分由一群非贴壁细胞组成，这些细胞表达不同强度的CD11c，至少可通过典型的DC形态（如具有面纱样细胞质树突的丰富细胞质、形状不规则的细胞核、多泡体和多层小体）、表面MHC II类分子的组成性水平、巨噬细胞特异性标志物（分别为F4/80、Mac-1和Fc受体）在CD11c+分选细胞亚群上的存在以及黏附分子和共刺激受体（如ICAM-1和CD44）的表达来表征。在原发性同种异体混合淋巴细胞反应（MLR）中证实了这种低密度CD11c+组分刺激T细胞反应的能力。在此，我们表明新鲜分离的CD11c+细胞显示出较弱的辅助功能，但在体外短期培养且存在粒细胞/巨噬细胞集落刺激因子的情况下会发展出这种能力。尽管分离出的CD11c+细胞的性质和功能能力需要进一步阐明，但这些描述表型和辅助功能的初步结果提供了一些证据，表明从PP分离出的这些细胞可能是未成熟形式的DC，并且作为抗原呈递细胞发挥关键作用，这对于理解调节肠道抗原摄取、处理和呈递的复杂网络具有重要意义。
