Moser Bernhard, Desai Dharmesh D, Downie Matthew P, Chen Yali, Yan Shi Fang, Herold Kevan, Schmidt Ann Marie, Clynes Raphael
Department of Medicine, Columbia University College of Physicians and Surgeons, New York, NY 10032, USA.
J Immunol. 2007 Dec 15;179(12):8051-8. doi: 10.4049/jimmunol.179.12.8051.
Receptor for advanced glycation end products (RAGE) is an activation receptor triggered by inflammatory S100/calgranulins and high mobility group box-1 ligands. We have investigated the importance of RAGE on Ag priming of T cells in murine models in vivo. RAGE is inducibly up-regulated during T cell activation. Transfer of RAGE-deficient OT II T cells into OVA-immunized hosts resulted in reduced proliferative responses that were further diminished in RAGE-deficient recipients. Examination of RAGE-deficient dendritic cells did not reveal functional impairment in Ag presentation, maturation, or migratory capacities. However, RAGE-deficient T cells showed markedly impaired proliferative responses in vitro to nominal and alloantigens, in parallel with decreased production of IFN-gamma and IL-2. These data indicate that RAGE expressed on T cells is required for efficient priming of T cells and elucidate critical roles for RAGE engagement during cognate dendritic cell-T cell interactions.
晚期糖基化终产物受体（RAGE）是一种由炎症性S100/钙粒蛋白和高迁移率族蛋白B1配体触发的激活受体。我们已经在体内小鼠模型中研究了RAGE对T细胞抗原启动的重要性。RAGE在T细胞激活过程中被诱导上调。将RAGE缺陷的OT II T细胞转移到经卵清蛋白免疫的宿主中，导致增殖反应降低，而在RAGE缺陷的受体中这种反应进一步减弱。对RAGE缺陷的树突状细胞的检查未发现其在抗原呈递、成熟或迁移能力方面存在功能障碍。然而，RAGE缺陷的T细胞在体外对名义抗原和同种异体抗原的增殖反应明显受损，同时干扰素-γ和白细胞介素-2的产生也减少。这些数据表明，T细胞上表达的RAGE是T细胞有效启动所必需的，并阐明了RAGE在同源树突状细胞-T细胞相互作用过程中的关键作用。
