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  Quorum Regulation via Nested Antagonistic Feedback Circuits Mediated by the Receptors CD28 and CTLA-4 Confers Robustness to T Cell Population Dynamics

Zenke, S., Palm, M. M., Braun, J., Gavrilov, A., Meiser, P., Böttcher, J. P., et al. (2020). Quorum Regulation via Nested Antagonistic Feedback Circuits Mediated by the Receptors CD28 and CTLA-4 Confers Robustness to T Cell Population Dynamics. Immunity, 52, 313-327. doi:10.1016/j.immuni.2020.01.018.

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Item Permalink: http://hdl.handle.net/21.11116/0000-0006-0877-C Version Permalink: http://hdl.handle.net/21.11116/0000-0006-0878-B
Genre: Journal Article

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 Creators:
Zenke, Simon1, Author
Palm, Margriet M.1, Author
Braun, Julia1, Author
Gavrilov, Alina2, Author
Meiser, Philippa1, Author
Böttcher, Jan P.1, Author
Beyersdorf, Niklas1, Author
Ehl, Stephan1, Author
Gerard, Audrey1, Author
Lämmermann, Tim2, Author              
Schumacher, Ton N.1, Author
Beltman, Joost B.1, Author
Rohr, Jan C.1, Author
Affiliations:
1External Organizations, ou_persistent22              
2Max Planck Institute of Immunobiology and Epigenetics, Max Planck Society, ou_1565141              

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Free keywords: CD28; CD80; CTLA-4; IL-2; T lymphocyte; feedback; population dynamics; quorum regulation; robustness
 Abstract: T cell responses upon infection display a remarkably reproducible pattern of expansion, contraction, and memory formation. If the robustness of this pattern builds entirely on signals derived from other cell types or if activated T cells themselves contribute to the orchestration of these population dynamics-akin to bacterial quorum regulation-is unclear. Here, we examined this question using time-lapse microscopy, genetic perturbation, bioinformatic predictions, and mathematical modeling. We found that ICAM-1-mediated cell clustering enabled CD8+ T cells to collectively regulate the balance between proliferation and apoptosis. Mechanistically, T cell expressed CD80 and CD86 interacted with the receptors CD28 and CTLA-4 on neighboring T cells; these interactions fed two nested antagonistic feedback circuits that regulated interleukin 2 production in a manner dependent on T cell density as confirmed by in vivo modulation of this network. Thus, CD8+ T cell-population-intrinsic mechanisms regulate cellular behavior, thereby promoting robustness of population dynamics.

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Language(s): eng - English
 Dates: 2020-02-18
 Publication Status: Published in print
 Pages: -
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 Table of Contents: -
 Rev. Type: Peer
 Identifiers: DOI: 10.1016/j.immuni.2020.01.018
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Title: Immunity
Source Genre: Journal
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Publ. Info: Cambridge, Mass. : Cell Press
Pages: - Volume / Issue: 52 Sequence Number: - Start / End Page: 313 - 327 Identifier: ISSN: 1074-7613
CoNE: https://pure.mpg.de/cone/journals/resource/954925604783