Mathematical modeling of lymphocyte kinetics reveals true residence times in and preferential migration of lymphocytes via ovine lymph nodes (CAM4P.157)

Abstract

Abstract There are many published values of lymphocyte residence times in lymph nodes of various mammals such as mice, rats, and sheep. Yet, most of these estimates have been obtained semiquantitatively, without the use of mathematical modeling, which raises a question about assumptions underlying such estimates. We developed a novel mathematical model for migration of lymphocytes in the whole body which takes into account the known biological details of how lymphocyte enter and exit major lymphoid tissues. We applied this novel mathematical model to experimental data on cannulation of different ovine lymph nodes (LNs). In particular, we predicted that in sheep, recirculatory lymphocytes spend on average 3 hours in the spleen and 20 hours in LNs with a distribution of residence times in LNs following a skewed gamma (lognormal-like) distribution. This is in contrast which a recent suggestion that the distribution of residence times of naïve T cells in murine LNs is exponential. We also found that lymphocytes isolated from the prescapular LN have a two-fold increased entrance rate into the prescapular LN as opposed to the intestinal LN. Importantly, the data could not be explained by preferential retention of cells in a specific LN. Taking together, our work illustrates the power of mathematical modeling in predicting the kinetics of lymphocyte migration in sheep and provides quantitative estimates of lymphocyte residence times in major ovine lymphoid tissues.