The dynamics of CD4+ T cell proliferation and regulation.

Abstract

We use mathematical modeling to study the proliferation dynamics of CD4+ T cells within an immune response. This proliferation is driven by the autocrine reaction of helper T cells and interleukin-2 (IL-2), and regulated by natural regulatory T cells (nTregs). Previous studies suggested that a fratricidal mechanism is necessary to eliminate helper T cells post-infection. Contrary to this, our mathematical analysis establishes that the depletion of these cells is due to two pivotal factors: the saturation in the proliferation rate of helper CD4+ T cells at high IL-2 concentrations, and the activation rate of nTregs outpacing their death rate. This yields an excitable process, such that the proliferation starts once the helper T cell population passes a threshold. Additionally, we find that when the proliferation of nTregs lags behind their mortality, induced regulatory T cells (iTregs) are crucial to curbing the proliferation of helper CD4+ T cells.