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

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...

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Podrobná bibliografia
Vydané v:	Immunity (Cambridge, Mass.) Ročník 52; číslo 2; s. 313
Hlavní autori:	Zenke, Simon, Palm, Margriet M, Braun, Julia, Gavrilov, Alina, Meiser, Philippa, Böttcher, Jan P, Beyersdorf, Niklas, Ehl, Stephan, Gerard, Audrey, Lämmermann, Tim, Schumacher, Ton N, Beltman, Joost B, Rohr, Jan C
Médium:	Journal Article
Jazyk:	English
Vydavateľské údaje:	United States 18.02.2020
Predmet:	Animals B7-1 Antigen - metabolism B7-2 Antigen - metabolism CD28 Antigens - metabolism CD8-Positive T-Lymphocytes - cytology CD8-Positive T-Lymphocytes - immunology CD8-Positive T-Lymphocytes - metabolism Cell Communication Cell Count Cell Line Cell Survival Cell Tracking CTLA-4 Antigen - metabolism Dendritic Cells - immunology Intercellular Adhesion Molecule-1 - metabolism Interleukin-2 - metabolism Lymphocyte Activation Mice Mice, Inbred C57BL Mice, Transgenic Models, Theoretical feedback CD80 CD28 robustness CTLA-4 IL-2 T lymphocyte quorum regulation population dynamics
ISSN:	1097-4180, 1097-4180
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Popis
Shrnutí:	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.
Bibliografia:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23
ISSN:	1097-4180 1097-4180
DOI:	10.1016/j.immuni.2020.01.018