CD8+ T Cells Orchestrate pDC-XCR1+ Dendritic Cell Spatial and Functional Cooperativity to Optimize Priming

Adaptive cellular immunity is initiated by antigen-specific interactions between T lymphocytes and dendritic cells (DCs). Plasmacytoid DCs (pDCs) support antiviral immunity by linking innate and adaptive immune responses. Here we examined pDC spatiotemporal dynamics during viral infection to uncover when, where, and how they exert their functions. We found that pDCs accumulated at sites of CD8+ T cell antigen-driven activation in a CCR5-dependent fashion. Furthermore, activated CD8+ T cells orchestrated the local recruitment of lymph node-resident XCR1 chemokine receptor-expressing DCs via secretion of the XCL1 chemokine. Functionally, this CD8+ T cell-mediated reorganization of the local DC network allowed for the interaction and cooperation of pDCs and XCR1+ DCs, thereby optimizing XCR1+ DC maturation and cross-presentation. These data support a model in which CD8+ T cells upon activation create their own optimal priming microenvironment by recruiting additional DC subsets to the site of initial antigen recognition. [Display omitted] •CXCR3 and CCR5 selectively control intranodal pDC migration•CD8+ T cells instruct pDC recruitment via CCL3 and CCL4•CD8+ T cells directly recruit XCR1+ DCs via XCL1•Active colocalization of XCR1+ DCs and pDCs supports DC cooperativity pDCs and XCR1+ dendritic cells are critical for the generation of antiviral CD8+ T cell responses. Brewitz and colleagues demonstrate that primed CD8+ T cells reorganize the intranodal dendritic cell network to optimize pDC and XCR1+ DC cooperativity and thereby enhance CD8+ T cell immunity.