Flt-3 ligand as adjuvant for DNA vaccination augments immune responses but does not skew TH1/TH2 polarization

Gene Ther. 2004 Jul;11(13):1048-56. doi: 10.1038/sj.gt.3302261.

Abstract

Since transfection of dendritic cells (DC) plays a key role in DNA vaccination, in vivo expansion of DC might be a tool to increase vaccine efficacy. We asked whether Fms-like tyrosine kinase-3 ligand (Flt-3L), a growth factor for DC, can be used as an adjuvant for DNA vaccination. Beta-galactosidase (beta-gal) was used as a model antigen in C57BL/6 mice. Mice were immunized i.m. with DNA coding for beta-gal with or without additional injection of Flt-3L. In both cases, antigen-specific CD4+ and CD8+ T cells were detectable after vaccination. Compared with DNA alone, additional administration of Flt-3L led to a significant increase in the antigen-specific proliferative response. However, increased cytotoxicity by T cells was not observed. The cytokines secreted by splenocytes of immunized mice upon in vitro stimulation with antigen had a TH2 profile. Humoral responses against beta-gal preferentially consisted of IgG1 antibodies. Analysis of DC from Flt-3L-treated mice revealed an immature phenotype with low or absent expression levels of CD80, CD86 and CD40. We conclude that Flt-3L does not generally skew immune responses towards a TH1 type. More likely, factors determined by the antigen and/or the vaccination procedure itself are crucial for the resulting type of immune response. Flt-3L - under circumstances such as the one we have investigated - can also lead to suppression of TH1 T cell immunity, possibly by expansion of immature/unactivated DC.

MeSH terms

  • Adjuvants, Immunologic / administration & dosage
  • Animals
  • Antibodies / blood
  • Cell Division
  • Dendritic Cells / immunology
  • Enzyme-Linked Immunosorbent Assay / methods
  • Female
  • Flow Cytometry
  • Immunoglobulin G / immunology
  • Immunohistochemistry
  • Injections, Intramuscular
  • Interferon-gamma / blood
  • Membrane Proteins / administration & dosage*
  • Mice
  • Mice, Inbred C57BL
  • Th1 Cells / immunology*
  • Th2 Cells / immunology*
  • Vaccines, DNA / administration & dosage*
  • beta-Galactosidase / genetics*
  • beta-Galactosidase / immunology

Substances

  • Adjuvants, Immunologic
  • Antibodies
  • Immunoglobulin G
  • Membrane Proteins
  • Vaccines, DNA
  • flt3 ligand protein
  • Interferon-gamma
  • beta-Galactosidase