Tissue-Specific Optimization of T Cell Activation in Draining Lymph Nodes
Nicole Pagane, Massachusetts Institute of Technology
There are dozens to hundreds of lymph nodes that exist in vertebrates that drain specific tissues. Since tissues have different functions and regenerative capacities, we hypothesize that immune activation in lymph nodes is regulated to effectively eliminate threats while concurrently avoiding irreparable damage to given tissues. If the proper balance is not maintained, there are drastic evolutionary fitness costs incurred upon the organism, such as death or infertility. To explore the trade-offs between host protection and tissue damage in different lymph nodes, we employ high-resolution multiplexed imaging and mathematical modeling to characterize the regulation of immune activation in different tissue sites. We assess spatial parameters of T cell activation in the spleen and several lymph nodes in Nur77GFP mice. In parallel, we construct a dynamic model of T cell activation that outputs the clonal expansion of T cells for a given antigen input and tissue-specific signals. We explore this system by posing the regulation of immune activation in different sites as a multi-objective optimization problem.
Abstract Author(s): Nicole Pagane