Glutamate released by dendritic cells as a novel modulator of T cell activation
Glutamate released by dendritic cells as a novel modulator of T cell activation
复制标题
DOI：
10.4049/jimmunol.177.10.6695
复制
发表时间：
2006-11-15
影响因子：
4.4
通讯作者：
Franco, Rafael
中科院分区：
文献类型：
--
作者：
Pacheco, Rodrigo;Oliva, Harold;Franco, Rafael
当树突状细胞(DC)将抗原呈递给T淋巴细胞，在次级淋巴器官中建立起生产性的免疫接触后，适应性免疫反应就开始了。尽管它与神经突触相似，但在T细胞-DC相互作用过程中，可溶性小非肽类介质参与细胞间串扰的研究仍然很少。在这项研究中，我们发现人类DC在成熟并与T细胞接触时会释放大量的谷氨酸，谷氨酸是哺乳动物的主要兴奋性神经递质。谷氨酸的释放是非囊泡性的，由DC表达的X-c(-)胱氨酸/谷氨酸逆向转运蛋白介导。DC来源的谷氨酸刺激结构性表达的代谢性谷氨酸受体5会削弱T细胞的激活。然而，在产生抗原提呈后，代谢性谷氨酸受体1在T细胞中表达，以促进T细胞的增殖和Th1和促炎细胞因子的分泌。这些数据表明，在T细胞-DC相互作用过程中，谷氨酸是启动T细胞介导的免疫反应的一种新的、高效的调节因子。
Adaptive immune responses begin after productive immunosynaptic contacts formation established in secondary lymphoid organs by dendritic cells (DC) presenting the Ag to T lymphocytes. Despite its resemblance to the neurosynapse, the participation of soluble small nonpeptidic mediators in the intercellular cross-talk taking place during T cell-DC interactions remains poorly studied. In this study, we show that human DC undergoing maturation and in contact with T cells release significant amounts of glutamate, which is the main excitatory neurotransmitter in mammalians. The release of glutamate is nonvesicular and mediated by the DC-expressed X-c(-) cystine/glutamate antiporter. DC-derived glutamate stimulating the constitutively expressed metabotropic glutamate receptor 5 impairs T cell activation. However, after productive Ag presentation, metabotropic glutamate receptor 1 is expressed in T cells to mediate enhanced T cell proliferation and secretion of Th1 and proinflammatory cytokines. These data suggest that, during T cell-DC interaction, glutamate is a novel and highly effective regulator in the initiation of T cell-mediated immune responses.