Redefining interferon-producing killer dendritic cells as a novel intermediate in NK-cell differentiation
Redefining interferon-producing killer dendritic cells as a novel intermediate in NK-cell differentiation
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DOI：
10.1182/blood-2011-11-395954
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发表时间：
2012-05-10
期刊：
影响因子：
20.3
通讯作者：
Lesage, Sylvie
中科院分区：
文献类型：
--
作者：
Guimont-Desrochers, Fanny;Boucher, Genevieve;Lesage, Sylvie
产生IFN的杀伤性树突状细胞（IKDC）具有显著的抗肿瘤活性，其细胞谱系起源一直存在争议。尽管IKDC最初被描述为同时表现出浆细胞样DC和自然杀伤（NK）细胞特性的细胞类型，但目前的观点反映IKDC仅代表表达B220的活化NK细胞，因此将其重命名为B220（+）NK细胞。在此，我们进一步研究了B220（+）NK细胞与其他NK细胞亚群的谱系关系。我们惊奇地发现，在过继转移后，B220（+）NK细胞没有获得B220表达，即使在存在有效激活刺激的情况下。这些发现有力地反驳了B220（+）NK细胞是活化的NK细胞的概念。此外，我们明确地表明，B220（+）NK细胞是高度增殖的，并在体内过继转移后分化为成熟的NK细胞。其他表型、功能和转录特征进一步将B220（+）NK细胞定义为成熟NK细胞的直接前体。对B220（+）NK细胞的这些新属性的表征将指导其在人类中的直系同源物的鉴定，有助于设计有效的癌症免疫疗法。（血。2012; 119（19）：4349-4357）
The cell lineage origin of IFN-producing killer dendritic cells (IKDCs), which exhibit prominent antitumoral activity, has been subject to debate. Although IKDCs were first described as a cell type exhibiting both plasmacytoid DC and natural killer (NK) cell properties, the current view reflects that IKDCs merely represent activated NK cells expressing B220, which were thus renamed B220(+) NK cells. Herein, we further investigate the lineage relation of B220(+) NK cells with regard to other NK-cell subsets. We surprisingly find that, after adoptive transfer, B220(+) NK cells did not acquire B220 expression, even in the presence of potent activating stimuli. These findings strongly argue against the concept that B220(+) NK cells are activated NK cells. Moreover, we unequivocally show that B220(+) NK cells are highly proliferative and differentiate into mature NK cells after in vivo adoptive transfer. Additional phenotypic, functional, and transcriptional characterizations further define B220(+) NK cells as immediate precursors to mature NK cells. The characterization of these novel attributes to B220(+) NK cells will guide the identification of their ortholog in humans, contributing to the design of potent cancer immunotherapies. (Blood. 2012; 119(19):4349-4357)