Mathematical Modeling Reveals Kinetics of Lymphocyte Recirculation in the Whole Organism
Figure 4
Increase in the average residence time of lymphocytes in lymph nodes with time since cannulation is needed to explain the kinetics of labeled lymphocyte exit during thoracic duct cannulation.
Cr-labeled TDLs were passaged via an intermediate host and then transferred into final recipient rats. Recipients were cannulated via the thoracic duct (Figure 1B) and the rate of exit of labeled TDLs into the thoracic duct per hour was measured [65]. The data are shown by markers (points). In panel A we show that for the parameter estimates from migration experiments (Table 1) the models with different number of subcompartments in LNs (
) fail to describe experimental data when
of lymphocytes exiting SCLNs migrate to the blood via the thoracic duct. To explain the data, we let the rate of lymphocyte exit from the LNs to decline exponentially with the time since cannulation,
(panel B). We fit the data on the output rate of labeled cells into the thoracic duct using the mathematical model (eqn. (1) – (6)). We fix all model parameters to values shown in parameters for
and fit only parameters
and
. The best description of the data was found when 1) the fraction
of lymphocytes in SCLNs enter the blood via the thoracic (left lymphatic) duct, and 2) the rate of lymphocyte migration via lymph nodes and Peyer's patches declines with time since cannulation at a rate
min
(solid line in panel B). The model fails to predict thoracic duct output data if residence times of lymphocytes in LNs is unaffected by cannulation (
, large dashing lines in panels A and B).