Ganusov Vitaly V, Auerbach Jeremy
Department of Microbiology, University of Tennessee, Knoxville, Tennessee, United States of America; Department of Mathematics, University of Tennessee, Knoxville, Tennessee, United States of America.
Department of Mathematics, University of Tennessee, Knoxville, Tennessee, United States of America.
PLoS Comput Biol. 2014 May 15;10(5):e1003586. doi: 10.1371/journal.pcbi.1003586. eCollection 2014 May.
The kinetics of recirculation of naive lymphocytes in the body has important implications for the speed at which local infections are detected and controlled by immune responses. With a help of a novel mathematical model, we analyze experimental data on migration of 51Cr-labeled thoracic duct lymphocytes (TDLs) via major lymphoid and nonlymphoid tissues of rats in the absence of systemic antigenic stimulation. We show that at any point of time, 95% of lymphocytes in the blood travel via capillaries in the lung or sinusoids of the liver and only 5% migrate to secondary lymphoid tissues such as lymph nodes, Peyer's patches, or the spleen. Interestingly, our analysis suggests that lymphocytes travel via lung capillaries and liver sinusoids at an extremely rapid rate with the average residence time in these tissues being less than 1 minute. The model also predicts a relatively short average residence time of TDLs in the spleen (2.5 hours) and a longer average residence time of TDLs in major lymph nodes and Peyer's patches (10 hours). Surprisingly, we find that the average residence time of lymphocytes is similar in lymph nodes draining the skin (subcutaneous LNs) or the gut (mesenteric LNs) or in Peyer's patches. Applying our model to an additional dataset on lymphocyte migration via resting and antigen-stimulated lymph nodes we find that enlargement of antigen-stimulated lymph nodes occurs mainly due to increased entrance rate of TDLs into the nodes and not due to decreased exit rate as has been suggested in some studies. Taken together, our analysis for the first time provides a comprehensive, systems view of recirculation kinetics of thoracic duct lymphocytes in the whole organism.
体内初始淋巴细胞再循环的动力学对于免疫反应检测和控制局部感染的速度具有重要意义。借助一个新颖的数学模型，我们分析了在无全身性抗原刺激情况下，51Cr标记的胸导管淋巴细胞（TDLs）通过大鼠主要淋巴组织和非淋巴组织迁移的实验数据。我们发现，在任何时间点，血液中95%的淋巴细胞通过肺毛细血管或肝脏血窦迁移，只有5%迁移至二级淋巴组织，如淋巴结、派尔集合淋巴结或脾脏。有趣的是，我们的分析表明，淋巴细胞通过肺毛细血管和肝脏血窦的迁移速度极快，在这些组织中的平均停留时间不到1分钟。该模型还预测TDLs在脾脏中的平均停留时间相对较短（2.5小时），而在主要淋巴结和派尔集合淋巴结中的平均停留时间较长（10小时）。令人惊讶的是，我们发现淋巴细胞在引流皮肤的淋巴结（皮下淋巴结）或肠道的淋巴结（肠系膜淋巴结）或派尔集合淋巴结中的平均停留时间相似。将我们的模型应用于另一组关于淋巴细胞通过静息和抗原刺激淋巴结迁移的数据集，我们发现抗原刺激淋巴结的肿大主要是由于TDLs进入淋巴结的速率增加，而不是如一些研究中所认为的由于出淋巴结速率降低。综上所述，我们的分析首次提供了对整个生物体中胸导管淋巴细胞再循环动力学的全面系统观点。
