Liver dendritic cells are less immunogenic than spleen dendritic cells because of differences in subtype composition

Liver dendritic cells are less immunogenic than spleen dendritic cells because of differences in subtype composition
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DOI:
10.4049/jimmunol.172.2.1009
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发表时间:
2004-01-15
影响因子:
4.4
通讯作者:
DeMatteo, RP
DeMatteo, RP
中科院分区:
医学2区
文献类型:
--
作者:
Pillarisetty, VG;Shah, AB;DeMatteo, RP

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肝脏独特的免疫学特性可能与肝脏树突状细胞(DC)的功能有关。然而,由于难以分离足够数量的细胞用于分析,肝脏树突状细胞的特征尚未得到很好的描述。用免疫磁珠和流式细胞仪对新鲜分离的小鼠肝和脾CD11c(+)DC进行比较。我们发现肝树突状细胞比脾树突状细胞成熟程度低,捕获的抗原更少,诱导的T细胞刺激也更少。然而,肝脏DC能够在CpG刺激下产生高水平的IL-12。基于广泛使用的DC亚群标记CD8pha和CD11b,我们确定了四种不同的肝脏DC亚型。淋巴系(CD8α(+)、CD11b(-))和髓样(CD8α-CD11b(+))肝树突状细胞激活T细胞的程度与脾树突状细胞相似,但仅占肝树突状细胞的20%。相反,两个更普遍的肝脏树突状细胞亚群只有微弱的免疫刺激作用。浆细胞样树突状细胞(B220(+))占肝脏树突状细胞的19%,但仅占脾树突状细胞的5%。我们的发现支持了广泛接受的观点,即肝脏DC通常是弱免疫激活剂,尽管它们能够产生炎性细胞因子,并且某些亚型可以有效地激活T细胞。
The unique immunological properties of the liver may be due to the function of hepatic dendritic cells (DC). However, liver DC have not been well characterized because of the difficulty in isolating adequate numbers of cells for analysis. Using immunomagnetic bead and flow cytometric cell sorting, we compared freshly isolated murine liver and spleen CD11c(+) DC. We found that liver DC are less mature, capture less Ag, and induce less T cell stimulation than spleen DC. Nevertheless, liver DC were able to generate high levels of IL-12 in response to CpG stimulation. We identified four distinct subtypes of liver DC based on the widely used DC subset markers CD8alpha and CD11b. Lymphoid (CD8alpha(+)CD11b(-)) and myeloid (CD8alpha-CD11b(+)) liver DC activated T cells to a similar degree as did their splenic DC counterparts but comprised only 20% of all liver DC. In contrast, the two more prevalent liver DC subsets were only weakly immunostimulatory. Plasmacytoid DC (B220(+)) accounted for 19% of liver DC, but only 5% of spleen DC. Our findings support the widely held notion that liver DC are generally weak activators of immunity, although they are capable of producing inflammatory cytokines, and certain subtypes potently activate T cells.