Maturation and activation of dendritic cells induced by lymphocyte activation gene-3 (CD223)
Maturation and activation of dendritic cells induced by lymphocyte activation gene-3 (CD223)
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DOI：
10.4049/jimmunol.168.8.3874
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发表时间：
2002-04-15
影响因子：
4.4
通讯作者：
Triebel, F
中科院分区：
文献类型：
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作者：
Andreae, S;Piras, F;Triebel, F
淋巴细胞激活基因 3 (LAG-3) 是在激活的 T 细胞和 NK 细胞上表达的 MHC II 类配体。 LAG-3Ig 融合蛋白已在小鼠中用作佐剂蛋白，以诱导抗肿瘤反应以及对名义 Ag 的特异性 CD8 和 CD4 Th1 反应。在这项工作中，我们报告了 LAG-3Ig 对人单核细胞来源的树突状细胞 (DC) 成熟和激活的影响。 LAG-3Ig 结合未成熟人类 DC 质膜脂筏中表达的 MHC II 类分子，并诱导快速形态变化，包括树突状突起的形成。 LAG-3Ig 显着上调共刺激分子的表达以及 IL-12 和 TNF-α 的产生。与这种对 DC 成熟的影响一致，LAG-3Ig 使 DC 无法捕获可溶性 Ag。这些事件与专业 APC 功能的获得有关，因为 LAG-3Ig 增加了 DC 刺激同种异体 T 细胞增殖和 IFN-γ 反应的能力。当使用特定 mAb 连接 MHC II 类时，未观察到这些效应。由天然配体 LAG-3 诱导的 II 类介导信号导致 DC 完全成熟，从而获得触发初始 T 细胞并驱动极化 Th1 反应的能力。
Lymphocyte activation gene-3 (LAG-3) is an MHC class II ligand expressed on activated T and NK cells. A LAG-3Ig fusion protein has been used in mice as an adjuvant protein to induce antitumor responses and specific CD8 and CD4 Th1 responses to nominal Ags. In this work we report on the effect of LAG-3Ig on the maturation and activation of human monocyte-derived dendritic cells (DC). LAG-3Ig binds MHC class II molecules expressed in plasma membrane lipid rafts on immature human DC and induces rapid morphological changes, including the formation of dendritic projections. LAG-3Ig markedly up-regulates the expression of costimulatory molecules and the production of IL-12 and TNF-alpha. Consistent with this effect on DC maturation, LAG-3Ig disables DC in their capacity to capture soluble Ags. These events are associated with the acquisition of professional APC function, because LAG-3Ig increases the capacity of DC to stimulate the proliferation and IFN-gamma response by allogeneic T cells. These effects were not observed when using ligation of MHC class II by specific mAb. Class II-mediated signals induced by a natural ligand, LAG-3, lead to complete maturation of DC, which acquire the capacity to trigger naive T cells and drive polarized Th1 responses.