Targeting Lymph Node Niches Enhances Type 1 Immune Responses to Immunization

• Main Authors: Jeffrey Lian, Aleksandra J. Ozga, Caroline L. Sokol, Andrew D. Luster
• Format: Article
• Language: English
• Published: Elsevier 2020-05-01
• Series: Cell Reports
• Subjects: vaccines; emulsification; lymph node; interfollicular region; chemokines; CXCL10
• Online Access: http://www.sciencedirect.com/science/article/pii/S221112472030632X

Summary: 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.