Unique functions of CD11b+, CD8α+, and double-negative Peyer's patch dendritic cells

Unique functions of CD11b+, CD8α+, and double-negative Peyer's patch dendritic cells
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DOI:
10.4049/jimmunol.166.8.4884
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发表时间:
2001-04-15
影响因子:
4.4
通讯作者:
Kelsall, BL
Kelsall, BL
中科院分区:
医学2区
文献类型:
--
作者:
Iwasaki, A;Kelsall, BL

文献摘要

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我们最近在小鼠Peyer's斑块中证明了三种树突状细胞(DC)的存在。CD11b(+)/CD8 α(-)(髓样)dc位于上皮下穹丘,CD11b(-)/CD8 α(+)(淋巴样)dc位于滤泡间区,CD11b(-)/CD8 α(-)(双阴性;DN) dc位于两个部位。我们现在描述了一种新的上皮内DN dc在滤泡相关上皮内的存在,并证明DN dc仅在粘膜淋巴组织中占主导地位。此外,我们证明所有DC亚群在体外成熟后保持其表面表型,并在暴露于T细胞和微生物刺激时分泌独特的细胞因子模式。只有来自PP的髓系dc在可溶性CD40配体(-)三聚体或金黄色葡萄球菌和ifn - γ刺激下产生高水平的IL-10。相比之下,淋巴和DN,而不是髓系DC,在微生物刺激后产生IL-12p70,而DC亚群在CD40配体三聚体的反应中没有产生IL-12p70。最后,我们发现,与来自非粘膜部位的细胞相比,来自PP的髓样dc特别能够启动初始T细胞分泌高水平的IL-4和IL-10,而来自所有组织的淋巴样和DN dc则启动ifn - γ的产生。因此,这些发现表明粘膜组织内的DC亚群具有独特的免疫诱导能力。
We have recently demonstrated the presence of three populations of dendritic cells (DC) in the murine Peyer's patch. CD11b(+)/CD8 alpha (-) (myeloid) DCs are localized in the subepithelial dome, CD11b(-)/CD8 alpha (+) (lymphoid) DCs in the interfollicular regions, and CD11b(-)/CD8 alpha (-) (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.