A Mathematical Model of the Primary T Cell Response with Contraction Governed by Adaptive Regulatory T Cells

Abstract

The currently accepted paradigm for the primary T cell response is that effector T cells commit to minimal developmental programs in which these cells expand according to some predetermined expansion program. Current mathematical models that are based on these developmental programs do not show the robustness to precursor frequencies that is exhibited in experimental results. Recently we proposed a shift in paradigm wherein the expansion and contraction of effector T cells is the result of negative feedback from adaptive regulatory T cells. These regulatory T cells develop in the course of an immune response and suppress effector cells. In this work, we extend our mathematical model to include regulation of helper T cells. Simulations show that this feedback mechanism generates robust immune responses over a range of five orders of magnitude of precursor frequencies.