title: Adequate immune response ensured by binary IL-2 and graded CD25 expression in a murine transfer model.
abstract: 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.
authors.affiliation: Robert Koch Institute, Berlin, Germany.|German Rheumatism Research Center Berlin (DRFZ), A Leibniz Institute, Berlin, Germany.
authors.forename: Franziska
authors.initials: F
authors.lastname: Fuhrmann
authors.affiliation: German Rheumatism Research Center Berlin (DRFZ), A Leibniz Institute, Berlin, Germany.
authors.forename: Timo
authors.identifier: 0000-0003-0413-4252
authors.initials: T
authors.lastname: Lischke
authors.affiliation: Institute for Theoretical Biology, Charité University Medicine, Berlin, Germany.
authors.forename: Fridolin
authors.initials: F
authors.lastname: Gross
authors.affiliation: German Rheumatism Research Center Berlin (DRFZ), A Leibniz Institute, Berlin, Germany.
authors.forename: Tobias
authors.initials: T
authors.lastname: Scheel
authors.affiliation: Robert Koch Institute, Berlin, Germany.|German Rheumatism Research Center Berlin (DRFZ), A Leibniz Institute, Berlin, Germany.
authors.forename: Laura
authors.initials: L
authors.lastname: Bauer
authors.affiliation: German Rheumatism Research Center Berlin (DRFZ), A Leibniz Institute, Berlin, Germany.
authors.forename: Khalid Wasim
authors.initials: KW
authors.lastname: Kalim
authors.affiliation: German Rheumatism Research Center Berlin (DRFZ), A Leibniz Institute, Berlin, Germany.|Charité University Medicine, Berlin, Germany.
authors.forename: Andreas
authors.initials: A
authors.lastname: Radbruch
authors.affiliation: Institute for Theoretical Biology, Charité University Medicine, Berlin, Germany.
authors.forename: Hanspeter
authors.identifier: 0000-0003-0414-7889
authors.initials: H
authors.lastname: Herzel
authors.affiliation: Robert Koch Institute, Berlin, Germany.|German Rheumatism Research Center Berlin (DRFZ), A Leibniz Institute, Berlin, Germany.
authors.forename: Andreas
authors.initials: A
authors.lastname: Hutloff
authors.affiliation: German Rheumatism Research Center Berlin (DRFZ), A Leibniz Institute, Berlin, Germany.
authors.forename: Ria
authors.identifier: 0000-0002-3289-1608
authors.initials: R
authors.lastname: Baumgrass
mesh_terms: D019264:Adoptive Transfer; D000818:Animals; D005786:Gene Expression Regulation; D007114:Immunization; D016130:Immunophenotyping; D007376:Interleukin-2 / Q000235:genetics* / Q000276:immunology; D053645:Interleukin-2 Receptor alpha Subunit / Q000235:genetics* / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D018448:Models, Immunological; D010047:Ovalbumin / Q000008:administration & dosage; D050799:STAT5 Transcription Factor / Q000235:genetics / Q000276:immunology; D015398:Signal Transduction; D059010:Single-Cell Analysis; D013602:T-Lymphocytes, Cytotoxic / Q000166:cytology / Q000187:drug effects / Q000276:immunology* / Q000637:transplantation; D006377:T-Lymphocytes, Helper-Inducer / Q000166:cytology / Q000187:drug effects / Q000276:immunology* / Q000637:transplantation; D050378:T-Lymphocytes, Regulatory / Q000166:cytology / Q000187:drug effects / Q000276:immunology*
chemical_list: D007376:Interleukin-2; D053645:Interleukin-2 Receptor alpha Subunit; D050799:STAT5 Transcription Factor; D010047:Ovalbumin
keywords: TCR signaling; Th cell activation; adaptive immune response; computational biology; cytokine expression; immunology; mouse; reaction-diffusion model; systems biology