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.

中文翻译：

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通过受体CD28和CTLA-4介导的嵌套拮抗反馈电路进行群体调控，使T细胞种群动态具有鲁棒性。

感染后的T细胞反应显示出显着可复制的扩张，收缩和记忆形成模式。如果这种模式的鲁棒性完全建立在源自其他细胞类型的信号上，或者激活的T细胞本身是否参与了这些种群动态的编排（类似于细菌群体调控），则尚不清楚。在这里，我们使用延时显微镜，遗传微扰，生物信息学预测和数学模型研究了这个问题。我们发现ICAM-1介导的细胞群集使CD8 + T细胞能够共同调节增殖和凋亡之间的平衡。从机理上讲，表达T细胞的CD80和CD86与相邻T细胞上的受体CD28和CTLA-4相互作用。这些相互作用为两个嵌套的拮抗性反馈回路提供了信号，该回路以依赖于T细胞密度的方式调节白介素2的产生，这在体内对该网络的调节中得到证实。因此，CD8 + T细胞内在调节机制调节细胞行为，从而促进种群动态的稳健性。