Targeting Lymph Node Niches Enhances Type 1 Immune Responses to Immunization

Generating robust CD4+ T-helper cell type 1 (Th1) responses is essential for protective vaccine-induced type 1 immunity. Here, we examine whether immunization formulation associated with enhanced vaccine efficacy promotes antigen targeting and cell recruitment into lymph node (LN) niches associated with optimal type 1 responses. Immunization with antigen and Toll-like receptor agonist emulsified in oil leads to an increased differentiation of IFNγ/TNF-α+ polyfunctional Th1 cells compared to an identical immunization in saline. Oil immunization results in a rapid delivery and persistence of antigen in interfollicular regions (IFRs) of the LN, whereas without oil, antigen is distributed in the medullary region. Following oil immunization, CXCL10-producing inflammatory monocytes accumulate in the IFR, which mobilizes antigen-specific CD4+ T cells into this niche. In this microenvironment, CD4+ T cells are advantageously positioned to encounter arriving IL-12-producing inflammatory dendritic cells (DCs). These data suggest that formulations delivering antigen to the LN IFR create an inflammatory niche that can improve vaccine efficacy. [Display omitted] •Oil emulsion targets antigen to the interfollicular region (IFR) of the lymph node•CXCL10+ monocytes accumulate in the IFR and attract antigen-specific CD4+ T cells•CD4+ T cells in the IFR are advantageously positioned to encounter IL-12+ DCs•Inflammatory niche in the IFR promotes IFNγ/TNF-α+ Th1 cells and type 1 immunity Lian et al. demonstrate that emulsification targets antigen/adjuvant to interfollicular regions of the lymph node. Infiltrating inflammatory monocytes localize to this specialized niche, where they produce CXCL10 and attract CD4+ T cells for advantageous positioning to encounter IL-12+ DCs, leading to the generation of enhanced type 1 immune responses.