ArticleProceedings of the National Academy of Sciences of the United States of America2012
Polyfunctional responses by human T cells result from sequential release of cytokines.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 179 papers.
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Who cites it
179 citing papers in PubMed.
- Trial
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- Combined Single-Cell Measurement of Cytokine mRNA and Protein in Immune Cells.Methods in molecular biology (Clifton, N.J.) · 2026Article
- Evaluation of single-cell heterogeneity and invasive potential in cancer cells via secreted protease activity assay.Analytica chimica acta · 2025Article
- Single-molecule imaging of transcription dynamics, RNA localization and fate in human T cells.The EMBO journal · 2025Article
- Multiplexed profiling of single-cell secretion on a hierarchical loading microwell chip.Biosensors & bioelectronics · 2025Article
- Heterologous DNA-Adenovirus Prime-Boost Strategy Expressing Bluetongue Virus VP2 and VP7 Proteins Protects Against Virulent Challenge.Vaccines · 2025Article
- Mapping the role of cytokine signaling at single-cell and structural resolution in uveal melanoma.Genes and immunity · 2025Article
- Temporal and spatial omics technologies for 4D profiling.Nature methods · 2025Review
- Proteogenomics Reveals Microproteins in Activated T Cells.Molecular & cellular proteomics : MCP · 2025Article
- Noncoding RNA (ncRNA)-mediated regulation of TLRs: critical regulator of inflammation in tumor microenvironment.Medical oncology (Northwood, London, England) · 2025Review
- iDC-targeting PfCSP mRNA vaccine confers superior protection against Plasmodium compared to conventional mRNA.NPJ vaccines · 2025Article
- Improving systemic delivery of oncolytic virus by cellular carriers.Cancer biology & medicine · 2025Review
119 more citing papers are in PubMed but not listed here.
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6 authors.
Funding
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.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.