Characterization of human DNGR-1+ BDCA3+ leukocytes as putative equivalents of mouse CD8alpha+ dendritic cells.

Characterization of human DNGR-1+ BDCA3+ leukocytes as putative equivalents of mouse CD8alpha+ dendritic cells.
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DOI:
10.1084/jem.20092618
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发表时间:
2010-06-07
期刊:
The Journal of experimental medicine
影响因子:
--
通讯作者:
Reis e Sousa C
Reis e Sousa C
中科院分区:
其他
文献类型:
--
作者:
Poulin LF;Salio M;Griessinger E;Anjos-Afonso F;Craciun L;Chen JL;Keller AM;Joffre O;Zelenay S;Nye E;Le Moine A;Faure F;Donckier V;Sancho D;Cerundolo V;Bonnet D;Reis e Sousa C

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在小鼠中,称为CD 8 α+ DCs的树突状细胞(DCs)亚群已成为调节T细胞应答的重要参与者和疫苗接种策略中有希望的靶点。然而,由于未能在人体中识别出CD 8 α+ DC,因此无法将其转化为临床方案。在这里,我们描述了一群表达DNGR-1(CLEC 9A)和高水平BDCA 3的人DC,其表型和功能与小鼠CD 8 α+ DC相似。我们描述了这种细胞在人类和人源化小鼠脾脏中的存在,并报告了在体外产生它们的方案。与小鼠CD 8 α+ DC一样,人DNGR-1+ BDCA 3 hi DC表达Necl 2、CD 207、BATF 3、IRF 8和TLR 3,但不表达CD 11b、IRF 4、TLR 7或(与CD 8 α+ DC不同)TLR 9。DNGR-1+ BDCA 3 hi DC对聚I:C和TLR 8的激动剂(但不对TLR 7的激动剂)有应答,并且当给予先天性和T细胞衍生的信号时产生白细胞介素(IL)-12。值得注意的是,来自体外培养的DNGR-1+ BDCA 3 + DC有效地内化来自死细胞的物质,并且在用聚I:C处理后可以将外源性抗原交叉呈递给CD 8 + T细胞。人DNGR-1+ BDCA 3 hi DC的表征和体外培养它们的能力为在免疫治疗中利用该亚群打开了大门。
In mouse, a subset of dendritic cells (DCs) known as CD8α+ DCs has emerged as an important player in the regulation of T cell responses and a promising target in vaccination strategies. However, translation into clinical protocols has been hampered by the failure to identify CD8α+ DCs in humans. Here, we characterize a population of human DCs that expresses DNGR-1 (CLEC9A) and high levels of BDCA3 and resembles mouse CD8α+ DCs in phenotype and function. We describe the presence of such cells in the spleens of humans and humanized mice and report on a protocol to generate them in vitro. Like mouse CD8α+ DCs, human DNGR-1+ BDCA3hi DCs express Necl2, CD207, BATF3, IRF8, and TLR3, but not CD11b, IRF4, TLR7, or (unlike CD8α+ DCs) TLR9. DNGR-1+ BDCA3hi DCs respond to poly I:C and agonists of TLR8, but not of TLR7, and produce interleukin (IL)-12 when given innate and T cell–derived signals. Notably, DNGR-1+ BDCA3+ DCs from in vitro cultures efficiently internalize material from dead cells and can cross-present exogenous antigens to CD8+ T cells upon treatment with poly I:C. The characterization of human DNGR-1+ BDCA3hi DCs and the ability to grow them in vitro opens the door for exploiting this subset in immunotherapy.
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