CCL19 and CCL21 induce a potent proinflammatory differentiation program in licensed dendritic cells
CCL19 and CCL21 induce a potent proinflammatory differentiation program in licensed dendritic cells
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DOI：
10.1016/j.immuni.2005.02.010
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发表时间：
2005-04-01
期刊：
影响因子：
32.4
通讯作者：
Bachmann, MF
中科院分区：
文献类型：
--
作者：
Marsland, BJ;Bättig, P;Bachmann, MF
树突状细胞（DC）是适应性免疫反应的关键激发者。使用甲病毒表达克隆技术，我们已确定趋化因子 CCL19 是 DC-T 细胞共培养系统中 T 细胞增殖的有效诱导剂。随后的研究表明，CCL19通过诱导DC成熟来增强T细胞增殖，导致共刺激分子上调和促炎细胞因子的产生。此外，CCL19 对 DC 进行编程以诱导 T 辅助细胞类型 (Th) 1 而不是 Th2 反应。重要的是，只有从外周迁移到引流淋巴结的活化 DC，而不是驻留在淋巴结内的静态 DC，在体内表达高水平的 CCR7，并对 CCL19 做出反应，产生促炎细胞因子。从 CCL19 和 CCL21 (plt/plt) 遗传缺陷的小鼠中分离出的迁移 DC 呈现出仅部分成熟的表型，突出了这些趋化因子对于体内 DC 完全成熟的重要性。我们的研究结果表明，CCL19 和 CCL21 是 DC 终末激活的有效天然佐剂，并且表明趋化因子不仅协调 DC 迁移，还调节其诱导 T 细胞反应的免疫原性潜力。
Dendritic cells (DCs) are key instigators of adaptive immune responses. Using an alphaviral expression cloning technology, we have identified the chemokine CCL19 as a potent inducer of T cell proliferation in a DC-T cell coculture system. Subsequent studies showed that CCL19 enhanced T cell proliferation by inducing maturation of DCs, resulting in upregulation of costimulatory molecules and the production of proinflammatory cytokines. Moreover, CCL19 programmed DCs for the induction of T helper type (Th) 1 rather than Th2 responses. Importantly, only activated DCs that migrated from the periphery to draining lymph nodes, but not resting steady-state DCs residing within lymph nodes, expressed high levels of CCR7 in vivo and responded to CCL19 with the production of proinflammatory cytokines. Migrating DCs isolated from mice genetically deficient in CCL19 and CCL21 (plt/plt) presented an only partially mature phenotype, highlighting the importance of these chemokines for full DC maturation in vivo. Our findings indicate that CCL19 and CCL21 are potent natural adjuvants for terminal activation of DCs and suggest that chemokines not only orchestrate DC migration but also regulate their immunogenic potential for the induction of T cell responses.