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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

MPS-Authors

Gavrilov,  Alina
Max Planck Institute of Immunobiology and Epigenetics, Max Planck Society;

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Lämmermann,  Tim
Max Planck Institute of Immunobiology and Epigenetics, Max Planck Society;

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Citation

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.


Cite as: http://hdl.handle.net/21.11116/0000-0006-0877-C
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.