T Lymphocytes Negatively Regulate Lymph Node Lymphatic Vessel Formation
T Lymphocytes Negatively Regulate Lymph Node Lymphatic Vessel Formation
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DOI：
10.1016/j.immuni.2010.12.016
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发表时间：
2011-01-28
期刊：
影响因子：
32.4
通讯作者：
Koh, Gou Young
中科院分区：
文献类型：
--
作者：
Kataru, Raghu P.;Kim, Honsoul;Koh, Gou Young
淋巴结淋巴管（LNLV）充当将抗原从外周组织引流到淋巴结内的管道。已知LNLV密度受B细胞、巨噬细胞和树突状细胞（DC）分泌的血管内皮生长因子的正调控。在这里，我们表明，LNLV的形成是负调控的T细胞。在稳定和炎症状态下，LNLV的密度在T细胞缺乏的情况下增加，但在T细胞恢复时减少。T细胞分泌的干扰素-γ抑制淋巴管内皮细胞中的淋巴细胞特异性基因，因此导致LNLV形成显著减少。当T细胞耗尽时，携带抗原的DC向LN的募集增加，反映了通过增加LNLV向T细胞呈递抗原的补偿机制。因此，T细胞通过干扰素-γ的负旁分泌作用维持LNLV密度的稳态平衡。
Lymph node lymphatic vessels (LNLVs) serve as a conduit to drain antigens from peripheral tissues to within the lymph nodes. LNLV density is known to be positively regulated by vascular endothelial growth factors secreted by B cells, macrophages, and dendritic cells (DCs). Here, we show that LNLV formation was negatively regulated by T cells. In both steady and inflammatory states, the density of LNLVs was increased in the absence of T cells but decreased when T cells were restored. Interferon-gamma secretion by T cells suppressed lymphatic-specific genes in lymphatic endothelial cells and consequently caused marked reduction in LNLV formation. When T cells were depleted, recruitment of antigen-carrying DCs to LNs was augmented, reflecting a compensatory mechanism for antigen presentation to T cells through increased LNLVs. Thus, T cells maintain the homeostatic balance of LNLV density through a negative paracrine action of interferon-gamma.