Maturation of monocyte-derived dendritic cells with Toll-like receptor 3 and 7/8 ligands combined with prostaglandin E2 results in high interleukin-12 production and cell migration.
Maturation of monocyte-derived dendritic cells with Toll-like receptor 3 and 7/8 ligands combined with prostaglandin E2 results in high interleukin-12 production and cell migration.
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DOI：
10.1007/s00262-008-0489-2
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发表时间：
2008-11
影响因子：
5.8
通讯作者：
de Vries, I. Jolanda M.
中科院分区：
文献类型：
--
作者：
Boullart, A. C. Inge;Aarntzen, Erik H. J. G.;Verdijk, Pauline;Jacobs, Joannes F. M.;Schuurhuis, Danita H.;Benitez-Ribas, Daniel;Schreibelt, Gerty;van de Rakt, Mandy W. M. M.;Scharenborg, Nicole M.;de Boer, Annemiek;Kramer, Matthijs;Figdor, Carl G.;Punt, Cornelis J. A.;Adema, Gosse J.;de Vries, I. Jolanda M.
关键词：
树突状细胞（DC）是免疫系统中专职的抗原呈递细胞，在调节基于T细胞的免疫中起关键作用。在体内，DC激活T细胞的能力取决于它们迁移到淋巴结的T细胞区域的能力以及它们的成熟状态。根据它们的肾上腺素分泌特征，DC能够在特定方向上扭曲免疫反应。特别地，产生IL-12 p70的DC驱动T细胞朝向T辅助1型应答。目前临床级离体产生的单核细胞衍生DC的严重缺点是IL-12 p70产生差。我们研究了Toll样受体（TLR）介导的成熟对体外产生的人单核细胞来源的DC的影响。我们证明，与精氨酸成熟的DC相反，用poly（I：C）（TLR 3配体）和/或R848（TLR 7/8配体）成熟的DC能够产生大量的IL-12 p70，但表现出降低的迁移能力。前列腺素E2（PGE 2）的加入改善了TLR-配体成熟DC的迁移能力，同时在T细胞相遇时维持它们的IL-12 p70产生。我们提出了一种新的临床级成熟方案，其中TLR配体poly（I：C）和R848与PGE 2组合以产生在T细胞相遇时具有高迁移能力和IL-12 p70产生的DC。本文的在线版本（doi：10.1007/s 00262 -008-0489-2）包含补充材料，可供授权用户使用。
Dendritic cells (DC) are professional antigen-presenting cells of the immune system that play a key role in regulating T cell-based immunity. In vivo, the capacity of DC to activate T cells depends on their ability to migrate to the T cell areas of lymph nodes as well as on their maturation state. Depending on their cytokine-secreting profile, DC are able to skew the immune response in a specific direction. In particular, IL-12p70 producing DC drive T cells towards a T helper 1 type response. A serious disadvantage of current clinical grade ex vivo generated monocyte-derived DC is the poor IL-12p70 production. We have investigated the effects of Toll-like receptor (TLR)-mediated maturation on ex vivo generated human monocyte-derived DC. We demonstrate that in contrast to cytokine-matured DC, DC matured with poly(I:C) (TLR3 ligand) and/or R848 (TLR7/8 ligand) are able to produce vast amounts of IL-12p70, but exhibit a reduced migratory capacity. The addition of prostaglandin E2 (PGE2) improved the migratory capacity of TLR-ligand matured DC while maintaining their IL-12p70 production upon T cell encounter. We propose a novel clinical grade maturation protocol in which TLR ligands poly(I:C) and R848 are combined with PGE2 to generate DC with both high migratory capacity and IL-12p70 production upon T cell encounter. The online version of this article (doi:10.1007/s00262-008-0489-2) contains supplementary material, which is available to authorized users.
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