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

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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 i.m. 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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Authors and Affiliations

  1. Department of Hematology, Oncology and Tumorimmunology, Charité – University Medicine Berlin, Campus Berlin-Buch, Berlin, Germany

    J Westermann, T Nguyen-Hoai, A Mollweide, G Richter, O Schmetzer, B Dörken & A Pezzutto

  2. Max Delbrück Center for Molecular Medicine, Berlin, Germany

    J Westermann, T Nguyen-Hoai, A Mollweide, G Richter, O Schmetzer, H-J Kim, Th Blankenstein, B Dörken & A Pezzutto

  3. Institute of Immunology, Charité – University Medicine Berlin, Campus Benjamin Franklin, Berlin, Germany

    Th Blankenstein

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  1. J Westermann
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  2. T Nguyen-Hoai
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Westermann, J., Nguyen-Hoai, T., Mollweide, A. et al. Flt-3 ligand as adjuvant for DNA vaccination augments immune responses but does not skew TH1/TH2 polarization. Gene Ther 11, 1048–1056 (2004). https://doi.org/10.1038/sj.gt.3302261

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  • DOI: https://doi.org/10.1038/sj.gt.3302261

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