CD86 and IL-12p70 are key players for T helper 1 polarization and natural killer cell activation by Toll-like receptor-induced dendritic cells.
CD86 and IL-12p70 are key players for T helper 1 polarization and natural killer cell activation by Toll-like receptor-induced dendritic cells.
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DOI：
10.1371/journal.pone.0044266
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发表时间：
2012
期刊：
影响因子：
3.7
通讯作者：
Subklewe M
中科院分区：
文献类型：
--
作者：
Lichtenegger FS;Mueller K;Otte B;Beck B;Hiddemann W;Schendel DJ;Subklewe M
树突状细胞（Dendritic cells，DC）通过表达共刺激分子和分泌细胞因子来决定T细胞的活化和极化。离体来源于单核细胞的DC的功能强烈依赖于所使用的成熟混合物的组成。我们分析了共刺激分子的表达和细胞因子分泌的DC T和自然杀伤（NK）细胞活化的影响进行头对头比较Toll样受体（TLR）激动剂为基础的鸡尾酒与标准组合的促炎细胞因子或IL-10单独。我们可以表明TLR诱导的DC的特征在于共刺激分子超过共抑制分子的优势和IL-12 p70的高分泌，但不是IL-10。在功能上，这些信号转化为分泌IFN-γ的Th 1细胞的增加和调节性T细胞的减少。T细胞活化和极化依赖于IL-12 p70和CD 86，但明显不依赖于CD 80信号传导。通过IL-12 p70的分泌，只有TLR诱导的DC激活NK细胞。TLR成熟的DC非常适合应用于依赖于强1型极化和NK细胞活化的免疫策略。它们的作用特别取决于高CD 86表达和IL-12 p70分泌。
Dendritic cells (DCs) determine the activation and polarization of T cells via expression of costimulatory molecules and secretion of cytokines. The function of DCs derived from monocytes ex vivo strongly depends on the composition of the maturation cocktail used. We analyzed the effect of costimulatory molecule expression and cytokine secretion by DCs on T and natural killer (NK) cell activation by conducting a head-to-head comparison of a Toll-like receptor (TLR) agonist-based cocktail with the standard combination of proinflammatory cytokines or IL-10 alone. We could show that TLR-induced DCs are characterized by a predominance of costimulatory over coinhibitory molecules and by high secretion of IL-12p70, but not IL-10. Functionally, these signals translated into an increase in IFN-γ secreting Th1 cells and a decrease in regulatory T cells. T cell activation and polarization were dependent on IL-12p70 and CD86, but remarkably not on CD80 signaling. By means of IL-12p70 secretion, only TLR-induced DCs activated NK cells. TLR-matured DCs are highly suitable for application in immunotherapeutic strategies that rely on strong type 1 polarization and NK cell activation. Their effects particularly depend on high CD86 expression and IL-12p70 secretion.
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DOI：
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