Revealing the role of the effector-regulatory t cell loop on autoimmune disease symptoms via nonlinear analysis

Abstract

In this paper, we investigate the influence of the effector-regulatory (Teff-Treg) T cell interaction on the T-cell-mediated autoimmune disease dynamics. The simple 3-dimensional Teff-Treg model is derived from the two-step model reduction of an established 5-dimensional model. The reduced 4- and 3-dimensional models preserve the dynamical behaviors in the original 5-dimensional model, which represents the chronic and relapse-remitting autoimmune symptoms. Moreover, we find three co-existing limit cycles in the reduced 3-dimensional model, in which two stable periodic solutions enclose an unstable one. The existence of multiple limit cycles provides a new mechanism to explain varying oscillating amplitudes of lesion grade in multiple sclerosis. The complex multiphase symptom could be caused by a noise-driven Teff population traveling between two coexisting stable periodic solutions. The simulated phase portrait and time history of coexisting limit cycles are given correspondingly.