Using microscopy, flow cytometry, adoptive cell transfer, and gene-modified mice, Lian et al. showed that emulsification of antigen (Ag) + Th1-skewing TLR4 agonist in incomplete Freund’s adjuvant rapidly, but passively, deposited s.c. injected Ag in cortical interfollicular regions (IFRs) ringing B cell areas of draining lymph nodes. CCL2 induced in IFRs attracted inflammatory monocytes, which became Ag+ and, when signaled by type I IFN, made CXCL10 to attract CD4+ T cells from the paracortex/T cell zone to the IFR/B cell areas. There, CD4+ T cells interacted with CCR7-dependent IL-12+DCSIGN+MHCII+ DC migrants to induce robust IFNγ/TNFα Th1 responses.
Contributed by Paula Hochman
ABSTRACT: 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 IFNgamma/TNF-alpha(+) 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.