Mouse strain differences in plasmacytoid dendritic cell frequency and function revealed by a novel monoclonal antibody

Mouse strain differences in plasmacytoid dendritic cell frequency and function revealed by a novel monoclonal antibody
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DOI:
10.4049/jimmunol.171.12.6466
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发表时间:
2003-12-15
影响因子:
4.4
通讯作者:
Trinchieri, G
Trinchieri, G
中科院分区:
医学2区
文献类型:
--
作者:
Asselin-Paturel, C;Brizard, G;Trinchieri, G

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在这项研究中,我们报告了一种新的大鼠单克隆抗体,识别小鼠浆细胞样树突状细胞(pDC)的一代。该抗体命名为12068,以高特异性染色一小部分CD11c(低)脾细胞。该群体在体外病毒刺激时产生大量的IFN-α。离体和体外衍生的120G8(+)细胞均显示与先前描述的小鼠pDC(B220(高)Ly6C(高)Gr1(低)CD11b(-)CD11c(低))相同的表型。用12068 mAb处理的小鼠耗尽了B220(高)Ly6C(高)CD11c(低)细胞,并且响应于体内CpG刺激产生IFN-α的能力大大降低。mAb 12068染色所有淋巴器官中的所有且仅染色B220(高)Ly6C(高)CD11c(低)pDC。用该mAb进行的免疫组织化学研究表明,pDC位于脾、淋巴结和派尔集合淋巴结的T细胞区域。虽然12068识别的抗原尚不清楚,但我们发现其表达被I型IFN在B细胞和DC上上调。在免疫荧光研究中使用这种mAb证明了pDC和其他DC亚群频率的菌株和器官特异性差异。与C57 BL/6小鼠相比,129 Sv小鼠在脾脏和血液中具有高得多的pDC频率,以及较低的常规CD8 α(+)CD11 c(高)DC频率。129Sv小鼠在体内产生IFN-α的较高能力与较高数量的pDC有关,但也与来自129Sv小鼠的pDC在体外响应病毒刺激产生IFN-α的较高能力有关。
We report in this study the generation of a novel rat mAb that recognizes mouse plasmacytoid dendritic cells (pDC). This Ab, named 12068, stains a small subset of CD11c(low) spleen cell with high specificity. This population produces high amounts of IFN-alpha upon in vitro viral stimulation. Both ex vivo- and in vitro-derived 120G8(+) cells display a phenotype identical with that of the previously described mouse pDC (B220(high)Ly6C(high)Gr1(low)CD11b(-)CD11c(low)). Mice treated with 12068 mAb are depleted of B220(high)Ly6C(high)CD11c(low) cells and have a much-reduced ability to produce IFN-alpha in response to in vivo CpG stimulation. The mAb 12068 stains all and only B220(high)Ly6C(high)CD11c(low) pDC in all lymphoid organs. Immunohistochemical studies performed with this mAb indicate that pDC are located in the T cell area of spleen, lymph nodes, and Peyer's patches. Although the Ag recognized by 12068 is not yet known, we show that its expression is up-regulated by type I IFN on B cells and DC. Using this mAb in immunofluorescence studies demonstrates strain- and organ-specific differences in the frequency of pDC and other DC subsets. 129Sv mice have a much higher frequency of pDC, together with a lower frequency of conventional CD8alpha(+)CD11c(high) DC, compared with C57BL/6 mice, both in spleen and blood. The higher ability of 129Sv mice to produce IFN-alpha in vivo is related to a higher number of pDC, but also to a higher ability of pDC from 129Sv mice to produce IFN-alpha in vitro in response to viral stimulation.