Andreae Susanne, Piras Fabienne, Burdin Nicolas, Triebel Frédéric
Laboratoire d'Immunologie des Tumeurs, Université Paris-Sud, Chatenay Malabry, France.
J Immunol. 2002 Apr 15;168(8):3874-80. doi: 10.4049/jimmunol.168.8.3874.
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.
淋巴细胞激活基因-3（LAG-3）是一种在活化的T细胞和NK细胞上表达的MHC II类配体。一种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抗原的特异性CD8和CD4 Th1反应。在这项工作中，我们报告了LAG-3Ig对人单核细胞衍生的树突状细胞（DC）成熟和活化的影响。LAG-3Ig与未成熟人DC质膜脂筏中表达的MHC II类分子结合，并诱导快速的形态变化，包括树突状突起的形成。LAG-3Ig显著上调共刺激分子的表达以及IL-12和TNF-α的产生。与对DC成熟的这种作用一致，LAG-3Ig使DC捕获可溶性抗原的能力丧失。这些事件与专业抗原呈递细胞功能的获得有关，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。当使用特异性单克隆抗体连接MHC II类时，未观察到这些效应。由天然配体LAG-3诱导的II类介导的信号导致DC完全成熟，DC获得触发初始T细胞并驱动极化Th1反应的能力。
