IL-10-generated tolerogenic dendritic cells are optimal for functional regulatory T cell induction - A comparative study of human clinical-applicable DC
IL-10-generated tolerogenic dendritic cells are optimal for functional regulatory T cell induction - A comparative study of human clinical-applicable DC
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DOI：
10.1016/j.clim.2011.11.011
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发表时间：
2012-03-01
影响因子：
8.6
通讯作者：
ten Brinke, Anja
中科院分区：
文献类型：
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作者：
Boks, Martine A.;Kager-Groenland, Judith R.;ten Brinke, Anja
致耐受性树突状细胞（Tolerogenic dendritic cells，tDC）是诱导移植免疫耐受和自身免疫的特异性细胞治疗工具。迄今为止，大多数描述的tDC方法尚未转化为临床适用的方案，并且缺乏对所需功能特征（即迁移和功能性调节性T细胞（Treg）诱导）的系统比较。我们比较了用维生素D-3、IL-10、地塞米松、TGF β或雷帕霉素产生的临床级tDC。为了获得良好的迁移能力和稳定的表型，需要额外的tDC成熟。用TNF α、IL-1 β和PGE（2）的混合物成熟诱导最佳迁移。重要的是，所有tDC在促炎条件下均显示稳定的表型。特别是IL-10 DC表现出最强的耐受性特征，具有高IL-10产生和低T细胞活化。此外，在功能抑制测定中，仅IL-10 DC诱导强烈抑制T细胞反应性的Treg。因此，临床级IL-10 DC显示出使其最适合耐受诱导疗法的功能特征。(C)2011 Elsevier Inc. All rights reserved.
Tolerogenic dendritic cells (tDC) are a promising tool for specific cellular therapy to induce immunological tolerance in transplantation and autoimmunity. To date, most described tDC methods have not been converted into clinically applicable protocols and systematic comparison of required functional characteristics, i.e. migration and functional regulatory T cell (Treg) induction, is lacking. We compare clinical-grade tDC generated with vitamin D-3, IL-10, dexamethasone, TGF beta, or rapamycin. For good migratory capacity and a stable phenotype, additional maturation of tDC was required. Maturation with a cocktail of TNF alpha, IL-1 beta and PGE(2) induced optimal migration. Importantly, all tDC showed a stable phenotype under proinflammatory conditions. Especially IL-10 DC showed most powerful tolerogenic characteristics with high IL-10 production and low T cell activation. Moreover, in a functional suppression assay only IL-10 DC induced Treg that strongly suppressed T cell reactivity. Thus, clinical-grade IL-10 DC show functional characteristics that make them best suited for tolerance-inducing therapies. (C) 2011 Elsevier Inc. All rights reserved.