| First Author | Zenke S | Year | 2020 |
| Journal | Immunity | Volume | 52 |
| Issue | 2 | Pages | 313-327.e7 |
| PubMed ID | 32049052 | Mgi Jnum | J:288519 |
| Mgi Id | MGI:6432179 | Doi | 10.1016/j.immuni.2020.01.018 |
| Citation | Zenke S, 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(2):313-327.e7 |
| abstractText | 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. |
