Strategically localized dendritic cells promote rapid T cell responses to lymph-borne particulate antigens

Immunity. 2015 Jan 20;42(1):172-85. doi: 10.1016/j.immuni.2014.12.024. Epub 2014 Dec 27.

Abstract

Upon infection, adaptive immune responses play catch-up with rapidly replicating pathogens. While mechanisms for efficient humoral responses to lymph-borne antigens have been characterized, the current paradigm for T cell responses to infections and particulate vaccines involves delayed migration of peripheral antigen-bearing dendritic cells (DCs) to lymph nodes (LNs), where they elicit effector T cell responses. Utilizing whole LN 3D imaging, histo-cytometry, and intravital 2-photon microscopy, we have identified a specialized population of DCs, enriched in the LN-resident CD11b(+) subset, which resides within the lymphatic sinus endothelium and scans lymph with motile dendrites. These DCs capture draining particles and present associated antigens to T lymphocytes, inducing T cell responses much sooner than and independently of migratory DCs. Thus, strategic DC subset positioning in LNs limits a potentially costly delay in generation of T cell responses to lymph-borne antigens, contributing to effective host defense. These findings are also highly relevant to vaccine design.

Publication types

  • Research Support, N.I.H., Intramural

MeSH terms

  • Animals
  • Antigen Presentation
  • Antigens, Bacterial / immunology
  • CD11b Antigen / metabolism
  • Cell Movement
  • Cells, Cultured
  • Dendrites / immunology
  • Dendritic Cells / immunology*
  • Endothelium, Lymphatic / immunology
  • Humans
  • Imaging, Three-Dimensional
  • Lymph Nodes / immunology
  • Lymphocyte Activation*
  • Mice
  • Mice, Inbred Strains
  • Mice, Transgenic
  • Particulate Matter / immunology
  • Pseudomonas aeruginosa / immunology*
  • T-Lymphocytes / immunology*
  • Vaccination

Substances

  • Antigens, Bacterial
  • CD11b Antigen
  • Particulate Matter