Spatio-temporal dynamics in cytokine signaling

6 October 2006

Thomas Höfer
Theoretical Biophysics Group
Humboldt University, Berlin


Regulatory T cells (Treg) prevent autoimmunity and contain immune responses by inhibiting conventional T cells. To survive and proliferate, Treg require the growth factor interleukin-2. Somewhat paradoxically, the IL-2 gene is repressed in Treg, while it is readily activated by antigen in conventional T cells. Thus, the two opposing cell types compete for cytokine produced by one of them. Both autocrine and paracrine actions of IL-2 are controlled by positive feedback loops. An experimentally-based mathematical model of this system shows rich dynamic behavior, including all-or-nothing responses to the antigen stimulus and strong distance sensitivity of competition. I will discuss the bifurcation analysis of the model, its implications for the interpretation of existing data, and first attempts to examine theoretical predictions experimentally. In the second part of the talk, I consider a model for cytokine signal transduction, leading to the nuclear accumulation of phosphorylated Stat transcription factors. Using quantitative data on the interferon-Stat1 pathway, the focus will be on the identification and experimental testing of critical steps in the molecular network that control nuclear Stat1 activity.

current theory lunch schedule