: The generation of effector CD8+ T cells (TEFF) requires activation of naïve CCR7+ T cells (TN) by dendritic cells (DCs) in lymphoid tissue. How TN-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 TEFF 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.

Lymphoid tissue chemokines limit priming duration to preserve CD8+ T cell functionality / Altenburger, L.M., Carvoeiro, D.C., Dehio, P., Zhou, J., Laura, C., Cuadros, À.B.I., Katoch, M., Krüger, C., De Albuquerque, J.B., Pfenninger, P., Magdaleno, J.M., Mehling, M., Iannacone, M., Gheinani, A.H., Dengjel, J., Abe, J., Stein, J.V.. - In: SCIENCE. - ISSN 0036-8075. - 392:6797(2026). [10.1126/science.adq2080]

Lymphoid tissue chemokines limit priming duration to preserve CD8+ T cell functionality

Laura C.;Iannacone M.;
2026-01-01

Abstract

: The generation of effector CD8+ T cells (TEFF) requires activation of naïve CCR7+ T cells (TN) by dendritic cells (DCs) in lymphoid tissue. How TN-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 TEFF 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.
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/20.500.11768/205836
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