Generation of Th1-Polarizing Dendritic Cells Using the TLR7/8 Agonist CL075
Generation of Th1-Polarizing Dendritic Cells Using the TLR7/8 Agonist CL075
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DOI：
10.4049/jimmunol.1000060
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发表时间：
2010-07-01
影响因子：
4.4
通讯作者：
Frankenberger, Bernhard
中科院分区：
文献类型：
--
作者：
Spranger, Stefani;Javorovic, Miran;Frankenberger, Bernhard
在本文中，我们描述了一种新的方法，用于制备人树突状细胞（DC），分泌生物活性IL-12（p70）使用合成的免疫刺激化合物作为TLR 7/8激动剂。单核细胞衍生的DC使用在3d内提供成熟细胞的程序产生。比较了含有各种细胞因子、IFN-γ、不同TLR激动剂和PGE（2）的几种成熟混合物对细胞恢复、表型、细胞因子分泌、迁移和淋巴细胞活化的影响。包括TLR 7/8激动剂R848或CL 075与TLR 3激动剂聚肌苷酸：聚胞苷酸组合的混合物产生分泌高水平IL-12（p70）的3-d成熟DC，其对CCR 7配体表现出强的趋化性，并且具有阳性共刺激潜力。它们还具有激活NK细胞、有效极化CD 4（+）和CD 8（+）T细胞以分泌IFN-γ和诱导T细胞介导的细胞毒性功能的优异能力。因此，使用这种成熟混合物在3天内制备的成熟DC显示出疫苗开发所需的最佳功能。免疫学杂志，2010，185：738-747。
In this paper, we describe a new method for preparation of human dendritic cells (DCs) that secrete bioactive IL-12(p70) using synthetic immunostimulatory compounds as TLR7/8 agonists. Monocyte-derived DCs were generated using a procedure that provided mature cells within 3 d. Several maturation mixtures that contained various cytokines, IFN-gamma, different TLR agonists, and PGE(2) were compared for impact on cell recovery, phenotype, cytokine secretion, migration, and lymphocyte activation. Mixtures that included the TLR7/8 agonists R848 or CL075, combined with the TLR3 agonist polyinosinic: polycytidylic acid, yielded 3-d mature DCs that secreted high levels of IL-12(p70), showed strong chemotaxis to CCR7 ligands, and had a positive costimulatory potential. They also had excellent capacity to activate NK cells, effectively polarized CD4(+) and CD8(+) T cells to secrete IFN-gamma and to induce T cell-mediated cytotoxic function. Thereby, mature DCs prepared within 3 d using such maturation mixtures displayed optimal functions required for vaccine development. The Journal of Immunology, 2010, 185: 738-747.