Oscillatory IL-2 stimulus reveals pertinent signaling timescales of T cell responsiveness.
Cell response to extracellular ligand is affected not only by ligand availability, but also by pre-existing cell-to-cell variability that enables a range of responses within a cell population. We developed a computational model that incorporates cell heterogeneity in order to investigate Jurkat T ce...
| Main Authors: | , |
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| Format: | Article |
| Language: | English |
| Published: |
Public Library of Science (PLoS)
2018-01-01
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| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC6143248?pdf=render |
| _version_ | 1819090412169592832 |
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| author | Linda E Kippner Melissa L Kemp |
| author_facet | Linda E Kippner Melissa L Kemp |
| author_sort | Linda E Kippner |
| collection | DOAJ |
| description | Cell response to extracellular ligand is affected not only by ligand availability, but also by pre-existing cell-to-cell variability that enables a range of responses within a cell population. We developed a computational model that incorporates cell heterogeneity in order to investigate Jurkat T cell response to time dependent extracellular IL-2 stimulation. Our model predicted preferred timing of IL-2 oscillatory input for maximizing downstream intracellular STAT5 nuclear translocation. The modeled cytokine exposure was replicated experimentally through the use of a microfluidic platform that enabled the parallelized capture of dynamic single cell response to precisely delivered pulses of IL-2 stimulus. The in vitro results demonstrate that single cell response profiles vary with pulsatile IL-2 input at pre-equilibrium levels. These observations confirmed our model predictions that Jurkat cells have a preferred range of extracellular IL-2 fluctuations, in which downstream response is rapidly initiated. Further investigation into this filtering behavior could increase our understanding of how pre-existing cellular states within immune cell populations enable a systems response within a preferred range of ligand fluctuations, and whether the observed cytokine range corresponds to in vivo conditions. |
| first_indexed | 2024-12-21T22:23:25Z |
| format | Article |
| id | doaj.art-fa406357c15f42829668ecb3fb42eba8 |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-21T22:23:25Z |
| publishDate | 2018-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-fa406357c15f42829668ecb3fb42eba82022-12-21T18:48:17ZengPublic Library of Science (PLoS)PLoS ONE1932-62032018-01-01139e020375910.1371/journal.pone.0203759Oscillatory IL-2 stimulus reveals pertinent signaling timescales of T cell responsiveness.Linda E KippnerMelissa L KempCell response to extracellular ligand is affected not only by ligand availability, but also by pre-existing cell-to-cell variability that enables a range of responses within a cell population. We developed a computational model that incorporates cell heterogeneity in order to investigate Jurkat T cell response to time dependent extracellular IL-2 stimulation. Our model predicted preferred timing of IL-2 oscillatory input for maximizing downstream intracellular STAT5 nuclear translocation. The modeled cytokine exposure was replicated experimentally through the use of a microfluidic platform that enabled the parallelized capture of dynamic single cell response to precisely delivered pulses of IL-2 stimulus. The in vitro results demonstrate that single cell response profiles vary with pulsatile IL-2 input at pre-equilibrium levels. These observations confirmed our model predictions that Jurkat cells have a preferred range of extracellular IL-2 fluctuations, in which downstream response is rapidly initiated. Further investigation into this filtering behavior could increase our understanding of how pre-existing cellular states within immune cell populations enable a systems response within a preferred range of ligand fluctuations, and whether the observed cytokine range corresponds to in vivo conditions.http://europepmc.org/articles/PMC6143248?pdf=render |
| spellingShingle | Linda E Kippner Melissa L Kemp Oscillatory IL-2 stimulus reveals pertinent signaling timescales of T cell responsiveness. PLoS ONE |
| title | Oscillatory IL-2 stimulus reveals pertinent signaling timescales of T cell responsiveness. |
| title_full | Oscillatory IL-2 stimulus reveals pertinent signaling timescales of T cell responsiveness. |
| title_fullStr | Oscillatory IL-2 stimulus reveals pertinent signaling timescales of T cell responsiveness. |
| title_full_unstemmed | Oscillatory IL-2 stimulus reveals pertinent signaling timescales of T cell responsiveness. |
| title_short | Oscillatory IL-2 stimulus reveals pertinent signaling timescales of T cell responsiveness. |
| title_sort | oscillatory il 2 stimulus reveals pertinent signaling timescales of t cell responsiveness |
| url | http://europepmc.org/articles/PMC6143248?pdf=render |
| work_keys_str_mv | AT lindaekippner oscillatoryil2stimulusrevealspertinentsignalingtimescalesoftcellresponsiveness AT melissalkemp oscillatoryil2stimulusrevealspertinentsignalingtimescalesoftcellresponsiveness |