A distinct priming phase regulates CD8 T cell immunity by orchestrating paracrine IL-2 signals

• 成果类型: Article
• 署名作者: Jobin, Katarzyna; Seetharama, Deeksha; Ruettger, Lennart; Fenton, Chloe; Kharybina, Ekaterina; Wirsching, Annerose; Huang, Anfei; Knoepper, Konrad; Kaisho, Tsuneyasu; Busch, Dirk H.; Vaeth, Martin; Saliba, Antoine-Emmanuel; Graw, Frederik; Pulfer, Alain; Gonzalez, Santiago F.; Zehn, Dietmar; Liang, Yinming; Ugur, Milas; Gasteiger, Georg; Kastenmueller, Wolfgang
• 署名单位: Max Planck Society; University of Wurzburg; Wakayama Medical University; Technical University of Munich; Helmholtz Association; Helmholtz-Center for Infection Research; University of Wurzburg; University of Erlangen Nuremberg; University of Erlangen Nuremberg; Universita della Svizzera Italiana; Technical University of Munich; Henan Medical University
• 刊物名称: SCIENCE
• ISSN/ISSBN: 0036-13005
• DOI: 10.1126/science.adq1405
• 发表日期: 2025-04-10
• 页码: 165-+
• 关键词: chemokine receptor cxcr3; dendritic cells; memory; effector; responses; differentiation; guidance; BEHAVIOR

摘要

T cell priming is characterized by an initial activation phase that involves stable interactions with dendritic cells (DCs). How activated T cells receive the paracrine signals required for their differentiation once they have disengaged from DCs and resumed their migration has been unclear. We identified a distinct priming phase that favors CD8 T cells expressing receptors with high affinity for antigen. CXCR3 expression by CD8 T cells was required for their hours-long reengagement with DCs in specific subfollicular niches in lymph nodes. CD4 T cells paused briefly at the sites of CD8 T cell and DC interactions and provided Interleukin-2 (IL-2) before moving to another DC. Our results highlight a previously unappreciated phase of cell-cell interactions during T cell priming and have direct implications for vaccinations and cellular immunotherapies.