Lewis X oligosaccharides targeting to DC-SIGN enhanced antigen-specific immune response

Immunology. 2007 Jun;121(2):174-82. doi: 10.1111/j.1365-2567.2007.02554.x. Epub 2007 Mar 20.

Abstract

Dendritic cell-specific intercellular-adhesion-molecule-grabbing non-integrin (DC-SIGN) is a potential target receptor for vaccination purposes. In the present study, we employed Lewis X (Le(x)) oligosaccharides, which mimic natural ligands, to target ovalbumin (OVA) to human dendritic cells (DCs) via DC-SIGN, to investigate the effect of this DC-SIGN-targeting strategy on the OVA-specific immune response. We demonstrated that Le(x) oligosaccharides could enhance the OVA-specific immune response as determined by enzyme-linked immunospot assay (ELISPOT), intracellular interferon-gamma staining and (51)Cr-release assay. An almost 300-fold lower dose of Le(x)-OVA induced balanced interferon-gamma-secreting cells compared to OVA alone. Furthermore, secretion of interleukin-10, a reported mediator of immune suppression related to DC-SIGN, was not increased by Le(x)-OVA, either alone or together with sCD40L-stimulated groups. A blocking antibody against DC-SIGN (12507) reduced the numbers of interferon-gamma-secreting cells during Le(x)-OVA stimulation, yet it did not prevent Le(x) oligosaccharides from promoting the secretion of interleukin-10 that was induced by ultra-pure lipopolysaccharide. These results suggested that the strategy of DC-SIGN targeting mediated by Le(x) oligosaccharides could promote a T-cell response. This DC-targeting may imply a novel vaccination strategy.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antigens / immunology
  • CD8-Positive T-Lymphocytes / immunology
  • Cell Adhesion Molecules / immunology*
  • Cell Differentiation / immunology
  • Cells, Cultured
  • Cytokines / metabolism
  • Dendritic Cells / immunology*
  • Dose-Response Relationship, Immunologic
  • Enzyme-Linked Immunosorbent Assay / methods
  • Epitopes, T-Lymphocyte / immunology
  • Humans
  • Interferon-gamma / biosynthesis
  • Interleukin-10 / biosynthesis
  • Lectins, C-Type / immunology*
  • Lewis Blood Group Antigens
  • Lymphocyte Activation / immunology
  • Oligosaccharides / immunology*
  • Ovalbumin / immunology
  • Receptors, Cell Surface / immunology*

Substances

  • Antigens
  • Cell Adhesion Molecules
  • Cytokines
  • DC-specific ICAM-3 grabbing nonintegrin
  • Epitopes, T-Lymphocyte
  • Lectins, C-Type
  • Lewis Blood Group Antigens
  • Lewis a oligosaccharide
  • Oligosaccharides
  • Receptors, Cell Surface
  • Interleukin-10
  • Interferon-gamma
  • Ovalbumin