Dynamical Modeling and Qualitative Analysis of a Delayed Model for CD8 T Cells in Response to Viral Antigens.

Abstract

Although the immune effector CD8 T cells play a crucial role in clearance of viruses, the mechanisms underlying the dynamics of how CD8 T cells respond to viral infection remain largely unexplored. Here, we develop a delayed model that incorporates CD8 T cells and infected cells to investigate the functional role of CD8 T cells in persistent virus infection. Bifurcation analysis reveals that the model has four steady states that can finely divide the progressions of viral infection into four states, and endows the model with bistability that has ability to achieve the switch from one state to another. Furthermore, analytical and numerical methods find that the time delay resulting from incubation period of virus can induce a stable low-infection steady state to be oscillatory, coexisting with a stable high-infection steady state in phase space. In particular, a novel mechanism to achieve the switch between two stable steady states, time-delay-based switch, is proposed, where the initial conditions and other parameters of the model remain unchanged. Moreover, our model predicts that, for a certain range of initial antigen load: 1) under a longer incubation period, the lower the initial antigen load, the easier the virus infection will evolve into severe state; while the higher the initial antigen load, the easier it is for the virus infection to be effectively controlled and 2) only when the incubation period is small, the lower the initial antigen load, the easier it is to effectively control the infection progression. Our results are consistent with multiple experimental observations, which may facilitate the understanding of the dynamical and physiological mechanisms of CD8 T cells in response to viral infections.