Cargando…
Single-cell quantification of IL-2 response by effector and regulatory T cells reveals critical plasticity in immune response
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 model...
Autores principales: | , , , , , , , , |
---|---|
Formato: | Texto |
Lenguaje: | English |
Publicado: |
European Molecular Biology Organization
2010
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3010113/ https://www.ncbi.nlm.nih.gov/pubmed/21119631 http://dx.doi.org/10.1038/msb.2010.90 |
_version_ | 1782194780834365440 |
---|---|
author | Feinerman, Ofer Jentsch, Garrit Tkach, Karen E Coward, Jesse W Hathorn, Matthew M Sneddon, Michael W Emonet, Thierry Smith, Kendall A Altan-Bonnet, Grégoire |
author_facet | Feinerman, Ofer Jentsch, Garrit Tkach, Karen E Coward, Jesse W Hathorn, Matthew M Sneddon, Michael W Emonet, Thierry Smith, Kendall A Altan-Bonnet, Grégoire |
author_sort | Feinerman, Ofer |
collection | PubMed |
description | 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. |
format | Text |
id | pubmed-3010113 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2010 |
publisher | European Molecular Biology Organization |
record_format | MEDLINE/PubMed |
spelling | pubmed-30101132010-12-27 Single-cell quantification of IL-2 response by effector and regulatory T cells reveals critical plasticity in immune response Feinerman, Ofer Jentsch, Garrit Tkach, Karen E Coward, Jesse W Hathorn, Matthew M Sneddon, Michael W Emonet, Thierry Smith, Kendall A Altan-Bonnet, Grégoire Mol Syst Biol Article 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. European Molecular Biology Organization 2010-11-30 /pmc/articles/PMC3010113/ /pubmed/21119631 http://dx.doi.org/10.1038/msb.2010.90 Text en Copyright © 2010, EMBO and Macmillan Publishers Limited https://creativecommons.org/licenses/by-nc-sa/3.0/This is an open-access article distributed under the terms of the Creative Commons Attribution Noncommercial Share Alike 3.0 Unported License, which allows readers to alter, transform, or build upon the article and then distribute the resulting work under the same or similar license to this one. The work must be attributed back to the original author and commercial use is not permitted without specific permission. |
spellingShingle | Article Feinerman, Ofer Jentsch, Garrit Tkach, Karen E Coward, Jesse W Hathorn, Matthew M Sneddon, Michael W Emonet, Thierry Smith, Kendall A Altan-Bonnet, Grégoire Single-cell quantification of IL-2 response by effector and regulatory T cells reveals critical plasticity in immune response |
title | Single-cell quantification of IL-2 response by effector and regulatory T cells reveals critical plasticity in immune response |
title_full | Single-cell quantification of IL-2 response by effector and regulatory T cells reveals critical plasticity in immune response |
title_fullStr | Single-cell quantification of IL-2 response by effector and regulatory T cells reveals critical plasticity in immune response |
title_full_unstemmed | Single-cell quantification of IL-2 response by effector and regulatory T cells reveals critical plasticity in immune response |
title_short | Single-cell quantification of IL-2 response by effector and regulatory T cells reveals critical plasticity in immune response |
title_sort | single-cell quantification of il-2 response by effector and regulatory t cells reveals critical plasticity in immune response |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3010113/ https://www.ncbi.nlm.nih.gov/pubmed/21119631 http://dx.doi.org/10.1038/msb.2010.90 |
work_keys_str_mv | AT feinermanofer singlecellquantificationofil2responsebyeffectorandregulatorytcellsrevealscriticalplasticityinimmuneresponse AT jentschgarrit singlecellquantificationofil2responsebyeffectorandregulatorytcellsrevealscriticalplasticityinimmuneresponse AT tkachkarene singlecellquantificationofil2responsebyeffectorandregulatorytcellsrevealscriticalplasticityinimmuneresponse AT cowardjessew singlecellquantificationofil2responsebyeffectorandregulatorytcellsrevealscriticalplasticityinimmuneresponse AT hathornmatthewm singlecellquantificationofil2responsebyeffectorandregulatorytcellsrevealscriticalplasticityinimmuneresponse AT sneddonmichaelw singlecellquantificationofil2responsebyeffectorandregulatorytcellsrevealscriticalplasticityinimmuneresponse AT emonetthierry singlecellquantificationofil2responsebyeffectorandregulatorytcellsrevealscriticalplasticityinimmuneresponse AT smithkendalla singlecellquantificationofil2responsebyeffectorandregulatorytcellsrevealscriticalplasticityinimmuneresponse AT altanbonnetgregoire singlecellquantificationofil2responsebyeffectorandregulatorytcellsrevealscriticalplasticityinimmuneresponse |