Human memory-like NK cells migrating to tuberculous pleural fluid via IP-10/CXCR3 and SDF-1/CXCR4 axis produce IFN-γ in response to Bacille Calmette Guerin
Human memory-like NK cells migrating to tuberculous pleural fluid via IP-10/CXCR3 and SDF-1/CXCR4 axis produce IFN-γ in response to Bacille Calmette Guerin
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DOI：
10.1016/j.clim.2013.04.003
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发表时间：
2013-07-01
影响因子：
8.6
通讯作者：
Wu, Changyou
中科院分区：
文献类型：
--
作者：
Fu, Xiaoying;Yang, Binyan;Wu, Changyou
我们之前已经证明，人类记忆样的NK细胞在结核性胸膜炎中持续存在，但尚不清楚NK细胞如何迁移到胸腔积液中。目前，我们发现来自结核胸腔积液细胞的NK细胞表达CXCR3和CXCR4的水平明显高于来自PBMC的NK细胞。迁移实验表明，IP-10和Sue-1诱导的NK细胞较PBMC有更多的迁移。将来自PFC的CD45RO(+)或CD45RO(-)NK细胞与自体单核细胞共培养，用卡介苗(BCG)刺激。结果表明，CD45RO(+)而不是CD45RO(-)的NK细胞产生较高水平的干扰素-γ，由于抗IL-12Rβ1单抗能显著抑制NK细胞产生的干扰素-γ，因此其产生的干扰素-γ是IL-12依赖的。综上所述，我们的研究结果表明，人类结核分枝杆菌特异性NK细胞主要通过IP-10/CXCR3和SDF-1/CXCR4轴向结核感染部位迁移，记忆样NK细胞可能在抗结核分支杆菌感染中发挥重要作用。(C)2013 Elsevier Inc.保留所有权利。
We have previously shown that human memory-like NK cells were persistent in tuberculous pleurisy but it was unclear how NK cells migrated into the pleural fluids. At present, we found that NK cells.from TB pleural fluid cells (PFCs) expressed significantly higher levels of CXCR3 and CXCR4 than NK cells from PBMCs. Migration assay demonstrated that IP-10 and SUE-1 induced more migration of NK cells from PFCs than PBMCs. CD45RO(+) or CD45RO(-) NK cells from PFCs were co-cultured with autologous monocytes and stimulated with BCG. The results showed CD45RO(+) but not CD45RO(-) NK cells produced significantly higher levels of IFN-gamma, which was IL-12-dependent since anti-IL-12R beta 1 mAbs could significantly inhibit the IFN-gamma by NK cells. Collectively, our data demonstrated that human Mycobacterium tuberculosis-specific NK cells were migrated into the local site of TB infection mainly via IP-10/CXCR3 and SDF-1/CXCR4 axis, memory-like NK cells might display an important role against M. tuberculosis infection. (C) 2013 Elsevier Inc. All rights reserved.