Rapid recirculation of migrating lymphocytes between blood, lung, and liver (173.26)

Abstract

Abstract Migration patterns of naive, effector, and memory lymphocytes have important implications for activation of primary and secondary immune responses and for efficient control of pathogens in peripheral tissues. Yet, quantitative details of how long it takes for lymphocytes to migrate from one tissue to another has been largely unknown. Using experimental data and mathematical modeling we estimate the rates of migration of thoracic duct lymphocytes (TDLs) from blood to multiple lymphoid and nonlymphoid tissues of a rat and back to the blood. Our model suggests extremely rapid recirculation of TDLs between blood, lung, and liver with an average residence time of cells in these tissues being less than 1 minute. The model also predicts longer residence times of TDLs in the spleen (2 hours) and major lymph nodes and Peyer's patches (8-10 hours). The same model provides a good match of independently measured output of TDLs via thoracic duct in cannulated animals. By comparing TDL accumulation in resting and antigen-stimulated lymph nodes we predict that enlargement of lymph nodes occurs because of increase entrance of lymphocytes into the inflamed LN and not decreased output as often viewed. Thus, we illustrate how within one modeling framework we can accurately describe multiple phenomena on lymphocyte recirculation in the whole organism.