Three-dimensional gradients of cytokine signaling between T cells
The adaptive immune system fights pathogens through the activation of immune cell clones that specifically recognize a particular pathogen. Tight contacts, so-called immunological synapses, of immune cells with cells that present ‘digested’ pathogen molecules are pivotal for ensuring specificity. Th...
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| Hauptverfasser: | , , , |
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| Dokumenttyp: | Article (Journal) |
| Sprache: | Englisch |
| Veröffentlicht: |
April 29, 2015
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| In: |
PLoS Computational Biology
Year: 2015, Jahrgang: 11, Heft: 4 |
| ISSN: | 1553-7358 |
| DOI: | 10.1371/journal.pcbi.1004206 |
| Online-Zugang: | Verlag, kostenfrei, Volltext: http://dx.doi.org/10.1371/journal.pcbi.1004206 Verlag, kostenfrei, Volltext: http://journals.plos.org/ploscompbiol/article/file?id=10.1371/journal.pcbi.1004206&type=printable Verlag, kostenfrei, Volltext: http://journals.plos.org/ploscompbiol/article?id=10.1371/journal.pcbi.1004206 
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| Verfasserangaben: | Kevin Thurley, Daniel Gerecht, Elfriede Friedmann, Thomas Höfer |
| Zusammenfassung: | The adaptive immune system fights pathogens through the activation of immune cell clones that specifically recognize a particular pathogen. Tight contacts, so-called immunological synapses, of immune cells with cells that present ‘digested’ pathogen molecules are pivotal for ensuring specificity. The discovery that immune responses are regulated by small diffusible proteins - the cytokines - has been surprising because cytokine diffusion to ‘bystander’ cells might compromise specificity. It has therefore been argued that cytokines are trapped in immunological synapses, whereas other authors have found that cytokines act on a larger scale through entire lymph nodes. Measurements of cytokine concentrations with fine spatial resolution have not been achieved. Here, we study the spatio-temporal dynamics of cytokines through mathematical analysis and three-dimensional numerical simulation and identify key parameters that control signaling range. We predict that even tight immunological synapses leak a substantial portion of the secreted cytokines. Nevertheless, rapid cellular uptake will render cytokine signals short-range and thus incidental activation of bystander cells can be limited. Long-range signals will only occur with multiple secreting cells or/and slow consumption by sparse target cells. Thus our study identifies key determinants of the spatial range of cytokine communication in realistic multicellular geometries. |
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| Beschreibung: | Gesehen am 31.08.2017 |
| Beschreibung: | Online Resource |
| ISSN: | 1553-7358 |
| DOI: | 10.1371/journal.pcbi.1004206 |