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    T-cell stimuli independently sum to regulate an inherited clonal division fate


    Marchingo, J.M. and Prevedello, G. and Kan, A. and Hodgkin, Philip D. and Duffy, Ken R. (2016) T-cell stimuli independently sum to regulate an inherited clonal division fate. Nature Communications, 7 (13540). ISSN 2041-1723

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    Abstract

    In the presence of antigen and costimulation, T cells undergo a characteristic response of expansion, cessation and contraction. Previous studies have revealed that population-level reproducibility is a consequence of multiple clones exhibiting considerable disparity in burst size, highlighting the requirement for single-cell information in understanding T-cell fate regulation. Here we show that individual T-cell clones resulting from controlled stimulation in vitro are strongly lineage imprinted with highly correlated expansion fates. Progeny from clonal families cease dividing in the same or adjacent generations, with inter-clonal variation producing burst-size diversity. The effects of costimulatory signals on individual clones sum together with stochastic independence; therefore, the net effect across multiple clones produces consistent, but heterogeneous population responses. These data demonstrate that substantial clonal heterogeneity arises through differences in experience of clonal progenitors, either through stochastic antigen interaction or by differences in initial receptor sensitivities.

    Item Type: Article
    Keywords: T-cell stimuli; regulate; inherited; clonal division fate;
    Academic Unit: Faculty of Science and Engineering > Research Institutes > Hamilton Institute
    Item ID: 8188
    Identification Number: https://doi.org/10.1038/ncomms13540
    Depositing User: Dr Ken Duffy
    Date Deposited: 03 May 2017 13:58
    Journal or Publication Title: Nature Communications
    Publisher: Nature Publshing Group
    Refereed: Yes
    URI:

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