PMID- 18800984 OWN - NLM STAT- MEDLINE DCOM- 20100125 LR - 20191210 IS - 1365-2567 (Electronic) IS - 0019-2805 (Print) IS - 0019-2805 (Linking) VI - 128 IP - 1 Suppl DP - 2009 Sep TI - 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. PG - e193-205 LID - 10.1111/j.1365-2567.2008.02947.x [doi] AB - 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 naive 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. FAU - Sudowe, Stephan AU - Sudowe S AD - Department of Dermatology, Johannes Gutenberg-University Mainz, Mainz, Germany. sudowe@mail.uni-mainz.de FAU - Dominitzki, Sabine AU - Dominitzki S FAU - Montermann, Evelyn AU - Montermann E FAU - Bros, Matthias AU - Bros M FAU - Grabbe, Stephan AU - Grabbe S FAU - Reske-Kunz, Angelika B AU - Reske-Kunz AB LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20080917 PL - England TA - Immunology JT - Immunology JID - 0374672 RN - 0 (Immunoglobulin G) RN - 0 (Interleukin-12 Subunit p40) RN - 0 (Keratin-15) RN - 0 (Keratin-5) RN - 0 (Krt15 protein, mouse) RN - 0 (Vaccines, DNA) RN - 37341-29-0 (Immunoglobulin E) RN - 82115-62-6 (Interferon-gamma) RN - EC 3.2.1.23 (beta-Galactosidase) SB - IM MH - Adoptive Transfer MH - Animals MH - *Antigen Presentation MH - *Biolistics MH - CD4-Positive T-Lymphocytes/immunology MH - CD8-Positive T-Lymphocytes/immunology MH - Cross-Priming/genetics/immunology MH - Cytotoxicity, Immunologic/genetics/immunology MH - Female MH - Genetic Vectors/immunology/metabolism MH - Hypersensitivity/*therapy MH - Immunoglobulin E/blood MH - Immunoglobulin G/blood MH - Interferon-gamma/genetics/immunology/metabolism MH - Interleukin-12 Subunit p40/genetics/immunology/metabolism MH - Keratin-15 MH - Keratin-5/immunology/metabolism MH - Keratinocytes/immunology MH - Langerhans Cells/*immunology MH - Mice MH - Mice, Knockout MH - Promoter Regions, Genetic/immunology MH - T-Lymphocytes, Helper-Inducer/enzymology/immunology MH - Vaccination/*methods MH - Vaccines, DNA/*administration & dosage/immunology MH - beta-Galactosidase/genetics PMC - PMC2753911 EDAT- 2008/09/20 09:00 MHDA- 2010/01/26 06:00 PMCR- 2010/09/01 CRDT- 2008/09/20 09:00 PHST- 2008/09/20 09:00 [pubmed] PHST- 2010/01/26 06:00 [medline] PHST- 2008/09/20 09:00 [entrez] PHST- 2010/09/01 00:00 [pmc-release] AID - IMM2947 [pii] AID - 10.1111/j.1365-2567.2008.02947.x [doi] PST - ppublish SO - Immunology. 2009 Sep;128(1 Suppl):e193-205. doi: 10.1111/j.1365-2567.2008.02947.x. Epub 2008 Sep 17.