Abstract
In this paper, we propose and analyse a mathematical model for the onset and development of autoimmune disease, with particular attention to stochastic effects in the dynamics. Stability analysis yields parameter regions associated with normal cell homeostasis, or sustained periodic oscillations. Variance of these oscillations and the effects of stochastic amplification are also explored. Theoretical results are complemented by experiments, in which experimental autoimmune uveoretinitis (EAU) was induced in B10.RIII and C57BL/6 mice. For both cases, we discuss peculiarities of disease development, the levels of variation in T cell populations in a population of genetically identical organisms, as well as a comparison with model outputs.
Highlights
To provide effective protection against various pathogenic challenges, the immune system should be able to successfully distinguish healthy cells from the cells infected by pathogens
We analysed the role of stochasticity in autoimmune dynamics, paying particular attention to the emergence of sustained stochastic oscillations in cell populations in individual realisations of the model, and showed how the variance of these stochastic oscillations depends on model parameters
These stochastic oscillations correspond to an autoimmune process, which can develop in the model when regulatory T cells do not sufficiently suppress autoreactive T cells
Summary
To provide effective protection against various pathogenic challenges, the immune system should be able to successfully distinguish healthy cells from the cells infected by pathogens. When this discrimination between self- and non-self fails, the immune system starts a specific attack on cells or organs, causing autoimmune disease. Iwami et al [10,11] analysed autoimmune dynamics emerging a result of breakdown of immune response to a viral infection, highlighting the importance of the function representing growth of susceptible host cells. Focusing on bystander activation as a mechanism of pathogen-induced autoimmunity, Burroughs et al [12,13,14] and Oliveira et al [15] analysed the role of interleukin-2 (IL-2)
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