Abstract
Effective immune surveillance depends on the continuous trafficking of CD8+ T cells between the circulation, lymphoid organs, and peripheral tissues. Although this homeostatic recirculation is well characterized, less is known about how these trafficking patterns change following immunization and T cell activation. In particular, it remains unclear whether immunization primarily alters trafficking locally within draining lymph nodes or produces broader changes in systemic recirculation, and whether naive and activated CD8+ T cells respond similarly. Here, we extended a previously validated stochastic model of naive CD8+ T cell recirculation in naive mice to naive and pre-activated OT-I CD8+ T cells co-transferred into mice that had been immunized with an attenuated strain of Toxoplasma gondii. Our previous work offered a set of migration parameters at homeostasis baseline that were initially applied to the immunized-host data. To accurately fit the recirculation data of naive T cells in the immunized mice, the model had to be changed by representing the draining lymph nodes separately and introducing an effective lymph-to-draining-lymph-node route. Activated cells required independent trafficking parameters and, in direct model-structure comparisons, both post-transfer cell division and the additional lymph-to-draining-lymph-node route improved agreement with the experimental data. Fitted activated cell parameters showed substantially reduced direct "blood" -to-lymph-node entry relative to naive cells, together with altered peripheral-tissue and splenic redistribution. These results show that immunization-associated and activation-dependent changes in CD8+ T cell distribution can be represented by extending a validated homeostatic recirculation framework while retaining much of its compartmental structure. However, identifiability of altered mechanisms remains a challenge. The inferred pathways should therefore be interpreted as effective trafficking mechanisms rather than direct anatomical measurements.