Polyfunctional responses by human T cells result from sequential release of cytokines
Name
Han-2012-Polyfunctional respo.pdf
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Author(s)
Bagheri, Nada
Lauffenburger, Douglas A.
Love, J. Christopher
Bradshaw, Elizabeth M.
Hafler, David A.
Han, Qing
Date Issued
December 2011
Journal
Proceedings of the National Academy of Sciences
Publisher
National Academy of Sciences
Citation
Han, Q. et al. “From the Cover: Polyfunctional Responses by Human T Cells Result from Sequential Release of Cytokines.” Proceedings of the National Academy of Sciences 109.5 (2011): 1607–1612. © 2011 National Academy of Sciences.
Version
Final published version
Abstract
The release of cytokines by T cells defines a significant part of their functional activity in vivo, and their ability to produce multiple cytokines has been associated with beneficial immune responses. To date, time-integrated end-point measurements have obscured whether these polyfunctional states arise from the simultaneous or successive release of cytokines. Here, we used serial, time-dependent, single-cell analysis of primary human T cells to resolve the temporal dynamics of cytokine secretion from individual cells after activation ex vivo. We show that multifunctional, Th1-skewed cytokine responses (IFN-γ, IL-2, TNFα) are initiated asynchronously, but the ensuing dynamic trajectories of these responses evolve programmatically in a sequential manner. That is, cells predominantly release one of these cytokines at a time rather than maintain active secretion of multiple cytokines simultaneously. Furthermore, these dynamic trajectories are strongly associated with the various states of cell differentiation suggesting that transient programmatic activities of many individual T cells contribute to sustained, population-level responses. The trajectories of responses by single cells may also provide unique, time-dependent signatures for immune monitoring that are less compromised by the timing and duration of integrated measures.
MIT Department
Massachusetts Institute of Technology. Department of Biological Engineering
Massachusetts Institute of Technology. Department of Chemical Engineering
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Article is made available in accordance with the publisher's policy and may be subject to US copyright law. Please refer to the publisher's site for terms of use.
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DOI of Published Version
https://doi.org/10.1073/pnas.1117194109
