IFN-producing killer dendritic cells are antigen-presenting cells endowed with T-cell cross-priming capacity.
IFN-producing killer dendritic cells are antigen-presenting cells endowed with T-cell cross-priming capacity.
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DOI：
10.1158/0008-5472.can-09-0508
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发表时间：
2009-08-15
期刊：
影响因子：
11.2
通讯作者：
Housseau F
中科院分区：
文献类型：
--
作者：
Pletneva M;Fan H;Park JJ;Radojcic V;Jie C;Yu Y;Chan C;Redwood A;Pardoll D;Housseau F
产生干扰素的杀伤树突状细胞 (IKDC) 代表了免疫系统中最近发现的一种细胞类型，它具有多种有助于先天性和适应性免疫的功能，包括产生 1 型和 2 型 IFN、IL-12、自然杀伤以及最终将抗原呈递给初始 T 细胞。在这里，我们比较了小鼠 IKDC、传统树突状细胞和自然杀伤细胞对小鼠巨细胞病毒感染的体外和体内反应，发现这些细胞亚群之间存在不同的功能。在识别受感染的成纤维细胞后，IKDC 以及 NK 产生高水平的 IFN-γ，但与 NK 不同的是，IKDC 同时产生 IL-12p40 并上调 MHC II 类和共刺激分子。使用 MHC-II 分子表达作为表型标记来区分激活的 IKDC 和激活的 NK，我们进一步证明，高度纯化的 MHC-II+ IKDC（而非 NK）在体外和体内将来自 MCMV 感染靶标的 MHC I 类限制性抗原交叉呈递给 CD8+ T 细胞。我们的研究结果强调了 IKDC 作为直接连接先天免疫和适应性免疫的杀伤抗原呈递细胞的独特性质。
Interferon-producing killer dendritic cells (IKDC) represent a recently discovered cell type in the immune system that possesses a number of functions contributing to innate and adaptive immunity, including production of type 1 and 2 IFNs, IL-12, natural killing, and ultimately antigen presentation to naïve T-cells. Here, we compared in vitro and in vivo responses of mouse IKDC, conventional dendritic cells and natural killer cells to murine cytomegalovirus infection and found distinct functions among these cell subsets. Upon recognition of infected fibroblasts, IKDC, as well as NK, produced high level of IFN-γ, but unlike NK, IKDC simultaneously produced IL-12p40 and upregulated MHC class II and costimulatory molecules. Using MHC-II molecule expression as a phenotypic marker to distinguish activated IKDC from activated NK, we further demonstrated that highly purified MHC-II+ IKDC but not NK, cross-present MHC class I-restricted antigens derived from MCMV-infected targets to CD8+ T-cells in vitro and in vivo. Our findings emphasize the unique nature of IKDC as a killer antigen presenting cell directly linking innate and adaptive immunity.