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

J Westermann, T Nguyen-Hoai, A Mollweide, G Richter… - Gene therapy, 2004 - nature.com
J Westermann, T Nguyen-Hoai, A Mollweide, G Richter, O Schmetzer, HJ Kim
Gene therapy, 2004nature.com
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 (β-gal) was used as a model antigen in C57BL/6 mice. Mice
were immunized im with DNA coding for β-gal with or without additional injection of Flt-3L. In
both cases, antigen-specific CD4+ and CD8+ T cells were detectable after vaccination …
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 (β-gal) was used as a model antigen in C57BL/6 mice. Mice were immunized im with DNA coding for β-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 β-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.
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