Abstracts (complete list) - Wissenschaft Online

Kevin Thurley, Dorothea Busse, Thomas Höfer
Spatiotemporal Cytokine Dynamics in T-Cell Regulation -
A Mathematical Model of IL-2• •Diffusion and Regulatory T-
Cells• (•Treg•)
Cytokine signalling is crucial for understanding the immune system.• •Up to now,•
•most knowledge has been based on ELISA studies,• •indicating extremely low•
(•picomolar•) •concentrations of cytokines.• •A classic calculation from diffusion-limited
reaction theory• (•Berg and Purcell,• •1972•) •shows that under such conditions,• •a
signal would take hours to occur.• •This raises the question how,• •nevertheless,•
•sensitive cytokine signalling in a noisy environment can be achieved.•
A two-dimensional reaction-diffusion model brings new insights to this question.• •We
consider a well-studied and physiologically important sample system:• •Activation of Thcells
via Interleukin(IL•)•-2• •and immunosuppression by Treg.• •The model reflects
experimentally proven features like autoactivation of Th-cells and low IL-2•
•concentrations in the bulk phase.• •Three major• •results have been obtained so far:•
•Firstly,• •the model predicts high local IL-2• •concentrations at secretion sites,•
•which can possibly be verified experimentally with quantitative secretion assays.•
•Thus,• •this property may serve to justify the model just as to explain effective signals
at low cytokine concentrations.• •Secondly,• •we can show a paracrine signal over
several cell diameters,• •confirming recent experimental results which suggest
paracrine rather than autocrine signalling in T-cell activation (Long and Adler,•
•2006•)•.• •And finally,• •immunosuppression by Treg may be explained by
competitive IL-2• •uptake.•
With the spatiotemporal modeling approach,• •we are able to predict the range of a
cytokine signal in dependence of important system parameters.• •Apparently,•
•inhomogeneities in the cytokine distribution are necessary to explain basic properties
of the complex cytokine network.•