No cell is an island: quorum-regulation of T cell behaviour by nested antagonistic feedback circuits

T cell responses upon infection display a remarkably reproducible pattern of expansion, contraction and memory formation. It is unclear, whether the robustness of this pattern builds entirely on signals derived from other cell types, or whether activated T cells themselves contribute to the orchestration of these population dynamics – akin to bacterial quorum-regulation. We examined this question and found that cell clustering enabled CD8+ T cells to collectively regulate the balance between proliferation and apoptosis. Mechanistically, this was mediated by two nested antagonistic feedback circuits, whose competition was modulated by T cell density. Such population-intrinsic regulation of cellular behavior promotes robustness of population dynamics.