Agent-based simulation of T-cell activation and proliferation within a lymph node.

Area of Science:

• Immunology
• Computational Biology
• Systems Biology

Background:

• Intravital microscopy reveals complex T cell behavior in lymph nodes.
• T cell response modeling requires integrating cell trafficking, motility, and activation processes.

Purpose of the Study:

• To develop an agent-based model integrating T cell trafficking, motility, and molecular signaling for T cell activation simulation.
• To account for spatiotemporal dynamics of T cell and dendritic cell interactions within lymph nodes.

Main Methods:

• An agent-based model simulating T cells in a 3D lymph node paracortex undergoing random walks.
• Integration of T cell signaling with dendritic cells (DCs) and proliferation.
• Inclusion of dynamic cell trafficking to model lymph node volume changes.

Main Results:

• The model simulates a large number of T cells at realistic densities.
• Simulated T cell proliferation kinetics and release match in vivo observations.
• The model captures changes in T cell avidity profiles consistent with experimental data.

Conclusions:

• The proposed modeling framework successfully simulates T cell activation, incorporating spatiotemporal T cell-DC interaction knowledge.
• The model can test the impact of parameter variations on T cell responses.
• Further refinement in collaboration with theoreticians and experimentalists is planned.