Pivotal role of dendritic cell-derived CXCL10 in the retention of T helper cell 1 lymphocytes in secondary lymph nodes.
Pivotal role of dendritic cell-derived CXCL10 in the retention of T helper cell 1 lymphocytes in secondary lymph nodes.
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DOI：
10.1084/jem.20011983
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发表时间：
2002-05-20
期刊：
影响因子：
--
通讯作者：
Matsushima K
中科院分区：
文献类型：
--
作者：
Yoneyama H;Narumi S;Zhang Y;Murai M;Baggiolini M;Lanzavecchia A;Ichida T;Asakura H;Matsushima K
各种免疫性疾病被认为是由辅助性T细胞（Th）1和Th 2亚群的平衡调节的。虽然Th淋巴细胞被认为是在引流淋巴结（LN）中产生的，但体内Th细胞在Th 1/Th 2极化过程中的行为在很大程度上未被探索。使用由痤疮丙酸杆菌诱导的小鼠肉芽肿性肝病模型，我们表明，在LN中的Th 1细胞的保留是由成熟树突状细胞（DC）产生的趋化因子CXCL 10/干扰素（IFN）诱导蛋白10控制的。抗原攻击后第7天，肝LN DC优先产生CXCL 10以吸引5′-溴-2 ′-脱氧尿苷（BrdU）+CD 4 + T细胞，并与产生IFN-γ的CD 4 + T细胞形成簇。阻断CXCL 10显著改变了形成簇的BrdU+ CD 4 + T细胞的分布。抗CXCL 10单克隆抗体治疗后，肝淋巴结中BrdU+ CD 4 + T细胞选择性减少，而循环中BrdU+ CD 4 + T细胞显著增加。同时伴有记忆性T细胞向肉芽肿周围的加速浸润，多数处于细胞周期，产生更多的IFN-γ，导致肝损伤加重。因此，成熟的DC衍生的CXCL 10对于将Th 1淋巴细胞保留在引流LN的T细胞区域内并优化Th 1介导的免疫应答是关键的。
Various immune diseases are considered to be regulated by the balance of T helper (Th)1 and Th2 subsets. Although Th lymphocytes are believed to be generated in draining lymph nodes (LNs), in vivo Th cell behaviors during Th1/Th2 polarization are largely unexplored. Using a murine granulomatous liver disease model induced by Propionibacterium acnes, we show that retention of Th1 cells in the LNs is controlled by a chemokine, CXCL10/interferon (IFN) inducible protein 10 produced by mature dendritic cells (DCs). Hepatic LN DCs preferentially produced CXCL10 to attract 5′-bromo-2′-deoxyuridine (BrdU)+CD4+ T cells and form clusters with IFN-γ–producing CD4+ T cells by day 7 after antigen challenge. Blockade of CXCL10 dramatically altered the distribution of cluster-forming BrdU+CD4+ T cells. BrdU+CD4+ T cells in the hepatic LNs were selectively diminished while those in the circulation were significantly increased by treatment with anti-CXCL10 monoclonal antibody. This was accompanied by accelerated infiltration of memory T cells into the periphery of hepatic granuloma sites, most of them were in cell cycle and further produced higher amount of IFN-γ leading to exacerbation of liver injury. Thus, mature DC-derived CXCL10 is pivotal to retain Th1 lymphocytes within T cell areas of draining LNs and optimize the Th1-mediated immune responses.
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影响因子：
56.9
作者：
Butcher, EC;Picker, LJ
通讯作者：
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影响因子：
56.9
作者：
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影响因子：
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作者：
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作者：
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Locksley, RM
DOI：
10.1084/jem.192.10.1515
发表时间：
2000-11-20
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
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通讯作者：
Gerard C