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by Dorothea Busse (Author)
This book adds to a intensively investigated question of immunological research. How do regulatory T cells mediate their function to ensure tolerance against self-antigen? The author analyzes the interaction via the cytokine interleukin 2 between T helper cells, which mediate immune responses, and regulatory T cells. Since both cell types depend on interleukin 2 to mediate their functions, competition for interleukin 2 is likely. A mathematical model is developed to describe the interaction. This model focuses on the interleukin 2 receptor dynamics on helper and regulatory T cells and the extracellular interleukin 2 diffusion. The interleukin 2 receptor dynamics is governed mainly by an autocrine positive feedback loop on both cell types. However, its differential regulation results in a switch-like up-regulation of the receptors on T helper cells and a gradual adaptation of the receptor levels to extracellular interleukin 2 supply on regulatory T cells. This difference enables regulatory T cells to efficiently compete for interleukin 2 and deprive T helper cells of their growth factor. Cell culture experiments verify these findings. It can be shown that the antigen stimulus and the intercellular distance are relevant control parameters for competition. Other mechanisms are described for suppression of T helper cell action by regulatory T cells; competition for interleukin 2 may act in concert with them.
