Lymph node cortical sinus organization and relationship to lymphocyte egress dynamics and antigen exposure
Lymph node cortical sinus organization and relationship to lymphocyte egress dynamics and antigen exposure
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DOI：
10.1073/pnas.1009968107
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发表时间：
2010-11-23
影响因子：
11.1
通讯作者：
Cyster, Jason G.
中科院分区：
文献类型：
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作者：
Grigorova, Irina L.;Panteleev, Mikhail;Cyster, Jason G.
最近的研究已经确定皮质窦作为鞘氨醇-1-磷酸受体-1（S1 P（1））依赖性T细胞和B细胞从淋巴结（LN）实质中流出的部位。然而，皮质窦在整个淋巴结中的分布以及其中淋巴流的范围尚不清楚。使用3D重建和活体双光子显微镜，我们描述了腹股沟LN内皮质窦网络的分支组织，并显示淋巴细胞流动开始于钝端窦内。许多皮质窦位于高内皮微静脉附近，一些淋巴细胞在进入LN后几分钟内进入这些窦。然而，一旦进入发炎的淋巴结，淋巴细胞迅速上调CD 69，并阻止进入皮质窦。使用LN重建数据和知识的淋巴细胞迁移和皮质窦进入动力学，我们开发了一个数学模型的T细胞出口淋巴结。该模型表明，随机游走遇到淋巴窦的主要因素，有助于LN通过时间。模型的预测和测得的通过时间之间的轻微差异可以解释为淋巴细胞在离开LN之前在实质和窦之间经历了几轮迁移。由于大的可溶性抗原能够快速进入皮质窦，这种实质-窦穿梭可能促进抗体应答。
Recent studies have identified cortical sinuses as sites of sphingosine-1-phosphate receptor-1 (S1P(1))-dependent T- and B-cell egress from the lymph node (LN) parenchyma. However, the distribution of cortical sinuses in the entire LN and the extent of lymph flow within them has been unclear. Using 3D reconstruction and intravital two-photon microscopy we describe the branched organization of the cortical sinus network within the inguinal LN and show that lymphocyte flow begins within blunt-ended sinuses. Many cortical sinuses are situated adjacent to high endothelial venules, and some lymphocytes access these sinuses within minutes of entering a LN. However, upon entry to inflamed LNs, lymphocytes rapidly up-regulate CD69 and are prevented from accessing cortical sinuses. Using the LN reconstruction data and knowledge of lymphocyte migration and cortical sinus entry dynamics, we developed a mathematical model of T-cell egress from LNs. The model suggests that random walk encounters with lymphatic sinuses are the major factor contributing to LN transit times. A slight discrepancy between predictions of the model and the measured transit times may be explained by lymphocytes undergoing a few rounds of migration between the parenchyma and sinuses before departing from the LN. Because large soluble antigens gain rapid access to cortical sinuses, such parenchyma-sinus shuttling may facilitate antibody responses.