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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...

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Main Authors: Helmstetter, Caroline (Author) , Flossdorf, Michael (Author) , Peine, Michael (Author) , Kupz, Andreas (Author) , Zhu, Jinfang (Author) , Hegazy, Ahmed N. (Author) , Duque-Correa, Maria A. (Author) , Zhang, Qin (Author) , Vainshtein, Yevhen (Author) , Radbruch, Andreas (Author) , Kaufmann, Stefan H. (Author) , Paul, William E. (Author) , Höfer, Thomas (Author) , Löhning, Max (Author)
Format: Article (Journal)
Language:English
Published: 2015
In: Immunity
Year: 2015, Volume: 42, Issue: 1, Pages: 108-122
ISSN:1097-4180
DOI:10.1016/j.immuni.2014.12.018
Online Access: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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Author Notes: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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Summary: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.
Item Description:Available online 25 December 2014
Gesehen am 17.08.2020
Physical Description:Online Resource
ISSN:1097-4180
DOI:10.1016/j.immuni.2014.12.018

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