Single-cell quantification of IL-2 response by effector and regulatory T cells reveals critical plasticity in immune response Journal Article

   

Authors:	Feinerman, O.; Jentsch, G.; Tkach, K. E.; Coward, J. W.; Hathorn, M. M.; Sneddon, M. W.; Emonet, T.; Smith, K. A.; Altan-Bonnet, G.
Article Title:	Single-cell quantification of IL-2 response by effector and regulatory T cells reveals critical plasticity in immune response
Abstract:	Understanding how the immune system decides between tolerance and activation by antigens requires addressing cytokine regulation as a highly dynamic process. We quantified the dynamics of interleukin-2 (IL-2) signaling in a population of T cells during an immune response by combining in silico modeling and single-cell measurements in vitro. We demonstrate that IL-2 receptor expression levels vary widely among T cells creating a large variability in the ability of the individual cells to consume, produce and participate in IL-2 signaling within the population. Our model reveals that at the population level, these heterogeneous cells are engaged in a tug-of-war for IL-2 between regulatory (T reg) and effector (T eff) T cells, whereby access to IL-2 can either increase the survival of T eff cells or the suppressive capacity of T reg cells. This tug-of-war is the mechanism enforcing, at the systems level, a core function of T reg cells, namely the specific suppression of survival signals for weakly activated T eff cells but not for strongly activated cells. Our integrated model yields quantitative, experimentally validated predictions for the manipulation of T reg suppression. © 2010 EMBO and Macmillan Publishers Limited.
Keywords:	controlled study; protein expression; nonhuman; methodology; cell proliferation; mouse; animal; metabolism; animals; mice; cell survival; cells, cultured; interleukin 2; biological model; models, biological; animal experiment; validation study; enzyme linked immunosorbent assay; mice, inbred c57bl; physiology; transgenic mouse; c57bl mouse; mice, transgenic; regulatory t lymphocyte; immunology; cellular immunity; immune response; regulatory mechanism; cell culture; t-lymphocytes, regulatory; staining; effector cell; upregulation; t-lymphocytes, helper-inducer; enzyme-linked immunosorbent assay; computer model; stat5 protein; cell activation; helper cell; interleukin-2; regulatory t cells; interleukin 2 receptor alpha; interleukin-2 receptor alpha subunit; staining and labeling; coculture; coculture techniques; immunity, cellular; plasticity; cellular heterogeneity; computer modeling; il-2 signaling; il2ra protein, mouse; single cell analysis; single-cell analysis
Journal Title:	Molecular Systems Biology
Volume:	6
ISSN:	1744-4292
Publisher:	Nature Publishing Group
Date Published:	2010-11-30
Start Page:	437
Language:	English
DOI:	10.1038/msb.2010.90
PUBMED:	21119631
PROVIDER:	scopus
PMCID:	PMC3010113
DOI/URL:	http://www.scopus.com/inward/record.url?eid=2-s2.0-78649875958&partnerID=40&md5=fcc7b01f1d8db16634d87a32cdd0ce0f
Notes:	--- - "Cited By (since 1996): 1" - "Export Date: 20 April 2011" - "Art. No.: 437" - "Source: Scopus"

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