期刊
CELL REPORTS
卷 31, 期 8, 页码 -出版社
CELL PRESS
DOI: 10.1016/j.celrep.2020.107679
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资金
- National Institutes of Health [CA204028]
- Cancer Research Institute
- American Association Cancer Research Basic Science Fellowships Program
- Swiss National Science Foundation Early Postdoctoral Mobility Award
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 IFN gamma/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.
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