Human CD141+ (BDCA-3)+ dendritic cells (DCs) represent a unique myeloid DC subset that cross-presents necrotic cell antigens.

Human CD141+ (BDCA-3)+ dendritic cells (DCs) represent a unique myeloid DC subset that cross-presents necrotic cell antigens.
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DOI:
10.1084/jem.20092140
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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:
Radford KJ
Radford KJ
中科院分区:
其他
文献类型:
--
作者:
Jongbloed SL;Kassianos AJ;McDonald KJ;Clark GJ;Ju X;Angel CE;Chen CJ;Dunbar PR;Wadley RB;Jeet V;Vulink AJ;Hart DN;Radford KJ

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人树突状细胞(DC)亚群的特性对于新疫苗的设计是必不可少的。我们报告的第一个详细的功能分析的人CD 141 + DC亚群。CD 141 + DC存在于人淋巴结、骨髓、扁桃体和血液中,后者被证明是用于功能分析的高度纯化的细胞的最佳来源。与更常研究的CD 1c + DC亚群相比,它们的特征在于高表达toll样受体3,产生IL-12 p70和IFN-β,以及诱导T辅助1细胞应答的上级能力。与poly I:C激活的CD 1c + DCs相比,poly I:C激活的CD 141 + DCs具有上级的向CD 8+细胞毒性T淋巴细胞交叉呈递可溶性蛋白抗原(Ag)的能力。重要的是,CD 141 + DCs,而不是CD 1c + DCs,被赋予了在它们摄取坏死病毒感染的细胞后交叉呈递病毒抗原的能力。这些发现确立了CD 141 + DC亚群是一种重要的功能独特的人DC亚型,其特征与小鼠CD 8 α+ DC亚群相似。这些数据证明了CD 141 + DC在诱导细胞毒性T淋巴细胞应答中的作用,并表明它们可能是针对癌症、病毒和其他病原体的疫苗接种的最相关靶点。
The characterization of human dendritic cell (DC) subsets is essential for the design of new vaccines. We report the first detailed functional analysis of the human CD141+ DC subset. CD141+ DCs are found in human lymph nodes, bone marrow, tonsil, and blood, and the latter proved to be the best source of highly purified cells for functional analysis. They are characterized by high expression of toll-like receptor 3, production of IL-12p70 and IFN-β, and superior capacity to induce T helper 1 cell responses, when compared with the more commonly studied CD1c+ DC subset. Polyinosine-polycytidylic acid (poly I:C)–activated CD141+ DCs have a superior capacity to cross-present soluble protein antigen (Ag) to CD8+ cytotoxic T lymphocytes than poly I:C–activated CD1c+ DCs. Importantly, CD141+ DCs, but not CD1c+ DCs, were endowed with the capacity to cross-present viral Ag after their uptake of necrotic virus-infected cells. These findings establish the CD141+ DC subset as an important functionally distinct human DC subtype with characteristics similar to those of the mouse CD8α+ DC subset. The data demonstrate a role for CD141+ DCs in the induction of cytotoxic T lymphocyte responses and suggest that they may be the most relevant targets for vaccination against cancers, viruses, and other pathogens.
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