In silico modelling of CD8 T cell immune response links genetic regulation to population dynamics

Abstract

The CD8 T cell immune response operates at multiple temporal and spatial scales, including all the early complex biochemical and biomechanical processes, up to long term cell population behavior.

In order to model this response, we devised a multiscale agent-based approach using Simuscale software. Within each agent (cell) of our model, we introduced a gene regulatory network (GRN) based upon a piecewise deterministic Markov process formalism. Cell fate – differentiation, proliferation, death – was coupled to the state of the GRN through rule-based mechanisms. Cells interact in a 3D computational domain and signal to each other via cell–cell contacts, influencing the GRN behavior.

Results show the ability of the model to correctly capture both population behavior and molecular time-dependent evolution. We examined the impact of several parameters on molecular and population dynamics, and demonstrated the add-on value of using a multiscale approach by showing the influence of molecular parameters, particularly protein degradation rates, on the outcome of the response, such as effector and memory cell counts.