T cells translate individual, quantal activation into collective, analog cytokine responses via time-integrated feedbacks
Variability within isogenic T cell populations yields heterogeneous ‘local’ signaling responses to shared antigenic stimuli, but responding clones may communicate ‘global’ antigen load through paracrine messengers, such as cytokines. Such coordination of individual cell responses within multicellula...
| Main Authors: | , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
eLife Sciences Publications Ltd
2014-04-01
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| Series: | eLife |
| Subjects: | |
| Online Access: | https://elifesciences.org/articles/01944 |
| _version_ | 1818018703374024704 |
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| author | Karen E Tkach Debashis Barik Guillaume Voisinne Nicole Malandro Matthew M Hathorn Jesse W Cotari Robert Vogel Taha Merghoub Jedd Wolchok Oleg Krichevsky Grégoire Altan-Bonnet |
| author_facet | Karen E Tkach Debashis Barik Guillaume Voisinne Nicole Malandro Matthew M Hathorn Jesse W Cotari Robert Vogel Taha Merghoub Jedd Wolchok Oleg Krichevsky Grégoire Altan-Bonnet |
| author_sort | Karen E Tkach |
| collection | DOAJ |
| description | Variability within isogenic T cell populations yields heterogeneous ‘local’ signaling responses to shared antigenic stimuli, but responding clones may communicate ‘global’ antigen load through paracrine messengers, such as cytokines. Such coordination of individual cell responses within multicellular populations is critical for accurate collective reactions to shared environmental cues. However, cytokine production may saturate as a function of antigen input, or be dominated by the precursor frequency of antigen-specific T cells. Surprisingly, we found that T cells scale their collective output of IL-2 to total antigen input over a large dynamic range, independently of population size. Through experimental quantitation and computational modeling, we demonstrate that this scaling is enforced by an inhibitory cross-talk between antigen and IL-2 signaling, and a nonlinear acceleration of IL-2 secretion per cell. Our study reveals how time-integration of these regulatory loops within individual cell signaling generates scaled collective responses and can be leveraged for immune monitoring. |
| first_indexed | 2024-04-14T07:42:19Z |
| format | Article |
| id | doaj.art-93b0bebb910d43acb92f2212db05dbe5 |
| institution | Directory Open Access Journal |
| issn | 2050-084X |
| language | English |
| last_indexed | 2024-04-14T07:42:19Z |
| publishDate | 2014-04-01 |
| publisher | eLife Sciences Publications Ltd |
| record_format | Article |
| series | eLife |
| spelling | doaj.art-93b0bebb910d43acb92f2212db05dbe52022-12-22T02:05:26ZengeLife Sciences Publications LtdeLife2050-084X2014-04-01310.7554/eLife.01944T cells translate individual, quantal activation into collective, analog cytokine responses via time-integrated feedbacksKaren E Tkach0Debashis Barik1Guillaume Voisinne2Nicole Malandro3Matthew M Hathorn4Jesse W Cotari5Robert Vogel6Taha Merghoub7Jedd Wolchok8Oleg Krichevsky9Grégoire Altan-Bonnet10Program in Computational Biology and Immunology, Memorial Sloan Kettering Cancer Center, New York, United States; Graduate program, Weill Cornell Medical College, New York, United StatesProgram in Computational Biology and Immunology, Memorial Sloan Kettering Cancer Center, New York, United StatesProgram in Computational Biology and Immunology, Memorial Sloan Kettering Cancer Center, New York, United StatesGraduate program, Weill Cornell Medical College, New York, United States; Immunology Program, Memorial Sloan Kettering Cancer Center, New York, United StatesProgram in Computational Biology and Immunology, Memorial Sloan Kettering Cancer Center, New York, United States; Graduate program, Weill Cornell Medical College, New York, United StatesProgram in Computational Biology and Immunology, Memorial Sloan Kettering Cancer Center, New York, United States; Graduate program, Weill Cornell Medical College, New York, United StatesProgram in Computational Biology and Immunology, Memorial Sloan Kettering Cancer Center, New York, United States; Graduate program, Weill Cornell Medical College, New York, United StatesImmunology Program, Memorial Sloan Kettering Cancer Center, New York, United StatesImmunology Program, Memorial Sloan Kettering Cancer Center, New York, United StatesPhysics Department, Ben Gurion University, Beer-Sheva, IsraelProgram in Computational Biology and Immunology, Memorial Sloan Kettering Cancer Center, New York, United States; Graduate program, Weill Cornell Medical College, New York, United StatesVariability within isogenic T cell populations yields heterogeneous ‘local’ signaling responses to shared antigenic stimuli, but responding clones may communicate ‘global’ antigen load through paracrine messengers, such as cytokines. Such coordination of individual cell responses within multicellular populations is critical for accurate collective reactions to shared environmental cues. However, cytokine production may saturate as a function of antigen input, or be dominated by the precursor frequency of antigen-specific T cells. Surprisingly, we found that T cells scale their collective output of IL-2 to total antigen input over a large dynamic range, independently of population size. Through experimental quantitation and computational modeling, we demonstrate that this scaling is enforced by an inhibitory cross-talk between antigen and IL-2 signaling, and a nonlinear acceleration of IL-2 secretion per cell. Our study reveals how time-integration of these regulatory loops within individual cell signaling generates scaled collective responses and can be leveraged for immune monitoring.https://elifesciences.org/articles/01944systems immunologyT lymphocyte activationcytokineself-organizationfeedback regulationimmune monitoring |
| spellingShingle | Karen E Tkach Debashis Barik Guillaume Voisinne Nicole Malandro Matthew M Hathorn Jesse W Cotari Robert Vogel Taha Merghoub Jedd Wolchok Oleg Krichevsky Grégoire Altan-Bonnet T cells translate individual, quantal activation into collective, analog cytokine responses via time-integrated feedbacks eLife systems immunology T lymphocyte activation cytokine self-organization feedback regulation immune monitoring |
| title | T cells translate individual, quantal activation into collective, analog cytokine responses via time-integrated feedbacks |
| title_full | T cells translate individual, quantal activation into collective, analog cytokine responses via time-integrated feedbacks |
| title_fullStr | T cells translate individual, quantal activation into collective, analog cytokine responses via time-integrated feedbacks |
| title_full_unstemmed | T cells translate individual, quantal activation into collective, analog cytokine responses via time-integrated feedbacks |
| title_short | T cells translate individual, quantal activation into collective, analog cytokine responses via time-integrated feedbacks |
| title_sort | t cells translate individual quantal activation into collective analog cytokine responses via time integrated feedbacks |
| topic | systems immunology T lymphocyte activation cytokine self-organization feedback regulation immune monitoring |
| url | https://elifesciences.org/articles/01944 |
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