TY - JOUR TI - Adequate immune response ensured by binary IL-2 and graded CD25 expression in a murine transfer model AU - Fuhrmann, Franziska AU - Lischke, Timo AU - Gross, Fridolin AU - Scheel, Tobias AU - Bauer, Laura AU - Kalim, Khalid Wasim AU - Radbruch, Andreas AU - Herzel, Hanspeter AU - Hutloff, Andreas AU - Baumgrass, Ria A2 - Dustin, Michael L VL - 5 PY - 2016 DA - 2016/12/30 SP - e20616 C1 - eLife 2016;5:e20616 DO - 10.7554/eLife.20616 UR - https://doi.org/10.7554/eLife.20616 AB - The IL-2/IL-2Ralpha (CD25) axis is of central importance for the interplay of effector and regulatory T cells. Nevertheless, the question how different antigen loads are translated into appropriate IL-2 production to ensure adequate responses against pathogens remains largely unexplored. Here we find that at single cell level, IL-2 is binary (digital) and CD25 is graded expressed whereas at population level both parameters show graded expression correlating with the antigen amount. Combining in vivo data with a mathematical model we demonstrate that only this binary IL-2 expression ensures a wide linear antigen response range for Teff and Treg cells under real spatiotemporal conditions. Furthermore, at low antigen concentrations binary IL-2 expression safeguards by its spatial distribution selective STAT5 activation only of closely adjacent Treg cells regardless of their antigen specificity. These data show that the mode of IL-2 secretion is critical to tailor the adaptive immune response to the antigen amount. KW - adaptive immune response KW - Th cell activation KW - TCR signaling KW - cytokine expression KW - systems biology KW - reaction-diffusion model JF - eLife SN - 2050-084X PB - eLife Sciences Publications, Ltd ER -