Altenburger et al. showed that although in vitro-activated CD8+ T cells that were attached to DCs for long periods exhibited persistent TCR signaling during cell division, in lymphoid tissue, DCs and T cells detached before T cell proliferation began. DC-attached T cells were transiently unresponsive, but regained CCR7 response to CCL19/21 over 24-48hrs to reposition F-actin-promoting factor DOCK2 away from the immune synapse and allow T cell detachment, effector gene transcription, and enhanced cytolysis. Prolonged DC–T cell interaction increased PD-1 and LAG3. Detachment favored increased effector function that lasted throughout the memory phase.
Contributed by Paula Hochman
ABSTRACT: The generation of effector CD8(+) T cells (T(EFF)) requires activation of nave CCR7(+) T cells (T(N)) by dendritic cells (DCs) in lymphoid tissue. How T(N)-DC interaction duration and signal integration are controlled remains unclear. In this study, we show that lymphoid stroma-secreted CCR7 ligands limit interaction duration by progressively inducing CD8(+) T cell release from DCs. At late interaction stages, CCR7 ligands relocalize the F-actin regulator DOCK2 away from the DC interface, permitting T cell detachment, proliferation onset, and acquisition of cytotoxicity. Disruption of CCR7 signaling causes prolonged T cell-DC contacts and produces dysfunctional T(EFF) with elevated inhibitory receptors, reduced antimicrobial activity, and impaired recall responses. Stromal chemokines therefore act as critical regulators of T cell priming by DCs, preserving CD8(+) effector function during acute and memory phases.
