Mathematical modeling suggests rapid migration of naive lymphocytes via lung capillaries and liver sinusoids (P5100)

Abstract

Abstract 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. In this study using mathematical modeling we analyze experimental data on migration of 51Cr-labeled thoracic duct lymphocytes (TDLs) via major lymphoid and nonlymphoid tissues of rats. We show that 95% of naive lymphocytes in the blood must travel via capillaries in the lung or sinusoids of the liver before they enter secondary lymphoid tissues. In contrast with a widespread belief that lymphocytes take long time to travel via vasculature of the lung and liver, 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 average residence time of lymphocytes is similar in lymph nodes draining skin (subcutaneous LNs), gut (mesenteric LNs) or in Peyer's patches.Taken together, our study for the first time provides a comprehensive, systems view of recirculation kinetics of naive lymphocytes in the whole organism.