Iwasaki A, Kelsall B L
Immune Cell Interaction Unit, Mucosal Immunity Section, Laboratory of Clinical Investigation, National Institutes of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
J Immunol. 2001 Apr 15;166(8):4884-90. doi: 10.4049/jimmunol.166.8.4884.
We have recently demonstrated the presence of three populations of dendritic cells (DC) in the murine Peyer's patch. CD11b(+)/CD8alpha(-) (myeloid) DCs are localized in the subepithelial dome, CD11b(-)/CD8alpha(+) (lymphoid) DCs in the interfollicular regions, and CD11b(-)/CD8alpha(-) (double-negative; DN) DCs at both sites. We now describe the presence of a novel population of intraepithelial DN DCs within the follicle-associated epithelium and demonstrate a predominance of DN DCs only in mucosal lymphoid tissues. Furthermore, we demonstrate that all DC subpopulations maintain their surface phenotype upon maturation in vitro, and secrete a distinct pattern of cytokines upon exposure to T cell and microbial stimuli. Only myeloid DCs from the PP produce high levels of IL-10 upon stimulation with soluble CD40 ligand(-) trimer, or Staphylococcus aureus and IFN-gamma. In contrast, lymphoid and DN, but not myeloid DCs, produce IL-12p70 following microbial stimulation, whereas no DC subset produces IL-12p70 in response to CD40 ligand trimer. Finally, we show that myeloid DCs from the PP are particularly capable of priming naive T cells to secrete high levels of IL-4 and IL-10, when compared with those from nonmucosal sites, while lymphoid and DN DCs from all tissues prime for IFN-gamma production. These findings thus suggest that DC subsets within mucosal tissues have unique immune inductive capacities.
我们最近证明，在小鼠派尔集合淋巴结中存在三种树突状细胞（DC）群体。CD11b(+)/CD8α(-)（髓样）DC定位于上皮下圆顶区，CD11b(-)/CD8α(+)（淋巴样）DC定位于滤泡间区，而CD11b(-)/CD8α(-)（双阴性；DN）DC在这两个部位均有分布。我们现在描述在滤泡相关上皮内存在一种新的上皮内DN DC群体，并证明DN DC仅在黏膜淋巴组织中占优势。此外，我们证明所有DC亚群在体外成熟后均保持其表面表型，并在暴露于T细胞和微生物刺激时分泌不同模式的细胞因子。只有来自派尔集合淋巴结的髓样DC在用可溶性CD40配体(-)三聚体、金黄色葡萄球菌或干扰素-γ刺激后产生高水平的白细胞介素-10。相反，淋巴样和DN DC（而非髓样DC）在微生物刺激后产生白细胞介素-12p70，而没有DC亚群在响应CD40配体三聚体时产生白细胞介素-12p70。最后，我们表明，与来自非黏膜部位的髓样DC相比，来自派尔集合淋巴结的髓样DC特别能够启动初始T细胞分泌高水平的白细胞介素-4和白细胞介素-10，而来自所有组织的淋巴样和DN DC则启动干扰素-γ的产生。因此，这些发现表明黏膜组织内的DC亚群具有独特的免疫诱导能力。
