A local regulatory T cell feedback circuit maintains immune homeostasis by pruning self-activated T cells.

ABSTRACT: A fraction of mature T cells can be activated by peripheral self-antigens, potentially eliciting host autoimmunity. We investigated homeostatic control of self-activated T cells within unperturbed tissue environments by combining high-resolution multiplexed and volumetric imaging with computational modeling. In lymph nodes, self-activated T cells produced interleukin (IL)-2, which enhanced local regulatory T cell (Treg) proliferation and inhibitory functionality. The resulting micro-domains reciprocally constrained inputs required for damaging effector responses, including CD28 co-stimulation and IL-2 signaling, constituting a negative feedback circuit. Due to these local constraints, self-activated T cells underwent transient clonal expansion, followed by rapid death ("pruning"). Computat

SUBMITTER: Wong HS 

PROVIDER: S-EPMC8390950 | biostudies-literature | 2021 Jul

REPOSITORIES: biostudies-literature