Trans-nodal migration of resident dendritic cells into medullary interfollicular regions initiates immunity to influenza vaccine

J Exp Med. 2014 Jul 28;211(8):1611-21. doi: 10.1084/jem.20132327. Epub 2014 Jul 21.

Abstract

Dendritic cells (DCs) are well established as potent antigen-presenting cells critical to adaptive immunity. In vaccination approaches, appropriately stimulating lymph node-resident DCs (LNDCs) is highly relevant to effective immunization. Although LNDCs have been implicated in immune response, their ability to directly drive effective immunity to lymph-borne antigen remains unclear. Using an inactive influenza vaccine model and whole node imaging approaches, we observed surprising responsiveness of LNDC populations to vaccine arrival resulting in a transnodal repositioning into specific antigen collection sites within minutes after immunization. Once there, LNDCs acquired viral antigen and initiated activation of viral specific CD4(+) T cells, resulting in germinal center formation and B cell memory in the absence of skin migratory DCs. Together, these results demonstrate an unexpected stimulatory role for LNDCs where they are capable of rapidly locating viral antigen, driving early activation of T cell populations, and independently establishing functional immune response.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antigen Presentation / immunology
  • Antigens, Viral / immunology
  • B-Lymphocytes / immunology
  • CD4-Positive T-Lymphocytes / immunology
  • Cell Movement / immunology*
  • Chemokines / metabolism
  • Cluster Analysis
  • Dendritic Cells / cytology*
  • Immunity / immunology*
  • Immunologic Memory / immunology
  • Influenza Vaccines / immunology*
  • Lymph / metabolism
  • Lymph Nodes / cytology*
  • Lymphocyte Activation / immunology
  • Mice
  • Mice, Inbred C57BL
  • Orthomyxoviridae / physiology
  • Orthomyxoviridae Infections / immunology
  • Orthomyxoviridae Infections / prevention & control
  • Orthomyxoviridae Infections / virology
  • Receptors, CXCR3 / metabolism
  • Species Specificity
  • Vaccination

Substances

  • Antigens, Viral
  • Chemokines
  • Cxcr3 protein, mouse
  • Influenza Vaccines
  • Receptors, CXCR3