Polyfunctional responses by human T cells result from sequential release of cytokines

Qing Han, Neda Bagheri, Elizabeth M. Bradshaw, David A. Hafler, Douglas A. Lauffenburger, J. Christopher Love*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

194 Scopus citations

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. Weshow 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.

Original languageEnglish (US)
Pages (from-to)1607-1612
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume109
Issue number5
DOIs
StatePublished - Jan 31 2012

Keywords

  • Computational biology
  • Dynamical systems
  • Microengraving
  • Multifunctionality

ASJC Scopus subject areas

  • General

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