Individual T helper cells have a quantitative cytokine memory
The probabilistic expression of cytokine genes in differentiated T helper (Th) cell populations remains ill defined. By single-cell analyses and mathematical modeling, we show that one stimulation featured stable cytokine nonproducers as well as stable producers with wide cell-to-cell variability in...
Gespeichert in:
| Hauptverfasser: | , , , , , , , , , , , , , |
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| Dokumenttyp: | Article (Journal) |
| Sprache: | Englisch |
| Veröffentlicht: |
2015
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| In: |
Immunity
Year: 2015, Jahrgang: 42, Heft: 1, Pages: 108-122 |
| ISSN: | 1097-4180 |
| DOI: | 10.1016/j.immuni.2014.12.018 |
| Online-Zugang: | Verlag, lizenzpflichtig, Volltext: https://doi.org/10.1016/j.immuni.2014.12.018 Verlag, lizenzpflichtig, Volltext: http://www.sciencedirect.com/science/article/pii/S1074761314004853 
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| Verfasserangaben: | Caroline Helmstetter, Michael Flossdorf, Michael Peine, Andreas Kupz, Jinfang Zhu, Ahmed N. Hegazy, Maria A. Duque-Correa, Qin Zhang, Yevhen Vainshtein, Andreas Radbruch, Stefan H. Kaufmann, William E. Paul, Thomas Höfer, Max Löhning |
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| 520 | |a The probabilistic expression of cytokine genes in differentiated T helper (Th) cell populations remains ill defined. By single-cell analyses and mathematical modeling, we show that one stimulation featured stable cytokine nonproducers as well as stable producers with wide cell-to-cell variability in the magnitude of expression. Focusing on interferon-γ (IFN-γ) expression by Th1 cells, mathematical modeling predicted that this behavior reflected different cell-intrinsic capacities and not mere gene-expression noise. In vivo, Th1 cells sort purified by secreted IFN-γ amounts preserved a quantitative memory for both probability and magnitude of IFN-γ re-expression for at least 1 month. Mechanistically, this memory resulted from quantitatively distinct transcription of individual alleles and was controlled by stable expression differences of the Th1 cell lineage-specifying transcription factor T-bet. Functionally, Th1 cells with graded IFN-γ production competence differentially activated Salmonella-infected macrophages for bacterial killing. Thus, individual Th cells commit to produce distinct amounts of a given cytokine, thereby generating functional intrapopulation heterogeneity. | ||
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