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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.

Original publication




Journal article



Publication Date





313 - 327.e7


CD28, CD80, CTLA-4, IL-2, T lymphocyte, feedback, population dynamics, quorum regulation, robustness, Animals, B7-1 Antigen, B7-2 Antigen, CD28 Antigens, CD8-Positive T-Lymphocytes, CTLA-4 Antigen, Cell Communication, Cell Count, Cell Line, Cell Survival, Cell Tracking, Dendritic Cells, Intercellular Adhesion Molecule-1, Interleukin-2, Lymphocyte Activation, Mice, Mice, Inbred C57BL, Mice, Transgenic, Models, Theoretical