A distinct priming phase regulates CD8 T cell immunity by orchestrating paracrine IL-2 signals
Katarzyna Jobin, Deeksha Seetharama, Lennart Rüttger, Chloe Fenton, Ekaterina Kharybina, Annerose Wirsching, Anfei Huang, Konrad Knöpper, Tsuneyasu Kaisho, Dirk H. Busch, Martin Vaeth, Antoine‐Emmanuel Saliba, Frederik Graw, Alain Pulfer, Santiago González, Dietmar Zehn, Yinming Liang, Milas Ugur, Georg Gasteiger, Wolfgang Kastenmüller
Abstract
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.