Uptake and presentation of exogenous antigen and presentation of endogenously produced antigen by skin dendritic cells represent equivalent pathways for the priming of cellular immune responses following biolistic DNA immunization.
Gene gun-mediated biolistic DNA vaccination with beta-galactosidase (betaGal)-encoding plasmid vectors efficiently modulated antigen-induced immune responses in an animal model of type I allergy, including the inhibition of immunoglobulin E (IgE) production. Here we show that CD4(+) as well as CD8(+) T cells from mice biolistically transfected with a plasmid encoding betaGal under the control of the fascin promoter (pFascin-betaGal) are capable of inhibiting betaGal-specific IgE production after adoptive transfer into naïve recipients. Moreover, suppression of IgE production was dependent on interferon (IFN)-gamma. To analyse the modalities of activation of CD4(+) and CD8(+) T cells regarding the localization of antigen synthesis following gene gun-mediated DNA immunization, we used the fascin promoter and the keratin 5 promoter (pK5-betaGal) to direct betaGal production mainly to dendritic cells (DCs) and to keratinocytes, respectively. Gene gun-mediated DNA immunization with each vector induced considerable activation of betaGal-specific CD8(+) cytotoxic T cells. Cytokine production by re-stimulated CD4(+) T cells in draining lymph nodes and immunoglobulin isotype profiles in sera of immunized mice indicated that immunization with pFascin-betaGal induced a T helper type 1 (Th1)-biased immune response, whereas immunization with pK5-betaGal generated a mixed Th1/Th2 immune response. Nevertheless, DNA vaccination with pFascin-betaGal and pK5-betaGal, respectively, efficiently inhibited specific IgE production in the mouse model of type I allergy. In conclusion, our data show that uptake of exogenous antigen produced by keratinocytes and its presentation by untransfected DCs as well as the presentation of antigen synthesized endogenously in DCs represent equivalent pathways for efficient priming of cellular immune responses.
Sudowe
Stephan
S
Department of Dermatology, Johannes Gutenberg-University Mainz, Mainz, Germany. sudowe@mail.uni-mainz.de
Dominitzki
Sabine
S
Montermann
Evelyn
E
Bros
Matthias
M
Grabbe
Stephan
S
Reske-Kunz
Angelika B
AB
D019264:Adoptive Transfer; D000818:Animals; D017951:Antigen Presentation; D019470:Biolistics; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D045142:Cross-Priming / Q000235:genetics / Q000276:immunology; D003602:Cytotoxicity, Immunologic / Q000235:genetics / Q000276:immunology; D005260:Female; D005822:Genetic Vectors / Q000276:immunology / Q000378:metabolism; D006967:Hypersensitivity / Q000628:therapy*; D007073:Immunoglobulin E / Q000097:blood; D007074:Immunoglobulin G / Q000097:blood; D007371:Interferon-gamma / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D053762:Interleukin-12 Subunit p40 / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D053569:Keratin-15; D053555:Keratin-5 / Q000276:immunology / Q000378:metabolism; D015603:Keratinocytes / Q000276:immunology; D007801:Langerhans Cells / Q000276:immunology*; D051379:Mice; D018345:Mice, Knockout; D011401:Promoter Regions, Genetic / Q000276:immunology; D006377:T-Lymphocytes, Helper-Inducer / Q000201:enzymology / Q000276:immunology; D014611:Vaccination / Q000379:methods*; D019444:Vaccines, DNA / Q000008:administration & dosage* / Q000276:immunology; D001616:beta-Galactosidase / Q000235:genetics
D007074:Immunoglobulin G; D053762:Interleukin-12 Subunit p40; D053569:Keratin-15; D053555:Keratin-5; C492053:Krt15 protein, mouse; D019444:Vaccines, DNA; D007073:Immunoglobulin E; D007371:Interferon-gamma; D001616:beta-Galactosidase
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