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

• 成果类型: Article
• 署名作者: Altenburger, Lukas M.; Carvoeiro, Daniela Claudino; Dehio, Philippe; Zhou, Jianwen; Laura, Chiara; Bofi I Cuadros, Alex; Katoch, Mitali; Kruger, Caroline; De Albuquerque, Juliana Barreto; Pfenninger, Petra; Magdaleno, Jose Martinez; Mehling, Matthias; Iannacone, Matteo; Gheinani, Ali Hashemi; Dengjel, Jorn; Abe, Jun; Stein, Jens V.
• 署名单位: University of Fribourg; University of Basel; University of Fribourg; Vita-Salute San Raffaele University; IRCCS Ospedale San Raffaele; University of Erlangen Nuremberg; Vita-Salute San Raffaele University; IRCCS Ospedale San Raffaele; University of Bern; University of Bern; University Hospital of Bern; Harvard University; Harvard Medical School
• 刊物名称: SCIENCE
• ISSN/ISSBN: 0036-8075; 1095-9203
• DOI: 10.1126/science.adq2080
• 发表日期: 2026-04-30
• 页码: eadq2080
• 关键词: FIBROBLASTIC RETICULAR CELLS; dendritic cells; EFFECTOR FUNCTION; clonal expansion; immune-response; RAC ACTIVATOR; antigen; motility; CCR7; ligands

摘要

The generation of effector CD8+ T cells (TEFF) requires activation of na & iuml;ve 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.