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* Christian Doppler Laboratory of Allergy Diagnostics and Therapy, Department of Molecular Biology, University Salzburg, Salzburg, Austria;
Department of Immunology, Bernhard-Nocht-Institute for Tropical Medicine, Hamburg, Germany;
Infection and Immunity Group, Centre for Cancer Research and Cell Biology, School of Biomedical Sciences, Queens University, Belfast, United Kingdom;
Centre d’Immunologie de Marseille-Luminy, Institut National de la Sante et de la Recherche Medicale-Centre National de la Recherche Scientifique, Marseille, France; and
¶ Department of Dermatology, Innsbruck Medical University, Innsbruck, Austria
Gene gun immunization, i.e., bombardment of skin with DNA-coated particles, is an efficient method for the administration of DNA vaccines. Direct transfection of APC or cross-presentation of exogenous Ag acquired from transfected nonimmune cells enables MHC-I-restricted activation of CD8+ T cells. Additionally, MHC-II-restricted presentation of exogenous Ag activates CD4+ Th cells. Being the principal APC in the epidermis, Langerhans cells (LC) seem ideal candidates to accomplish these functions. However, the dependence on LC of gene gun-induced immune reactions has not yet been demonstrated directly. This was primarily hampered by difficulties to discriminate the contributions of LC from those of other dermal dendritic cells. To address this problem, we have used Langerin-diphtheria toxin receptor knockin mice that allow for selective inducible ablation of LC. LC deficiency, even over the entire duration of experiments, did not affect any of the gene gun-induced immune functions examined, including proliferation of CD4+ and CD8+ T cells, IFN-
secretion by spleen cells, Ab production, CTL activity, and development of protective antitumor immunity. Together, our data show that gene gun immunization is capable of inducing humoral and cell-mediated immune reactions independently of LC.
The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
1 This work was supported, in parts, by Fonds zur Forderung der Wissenschaftlichen Forschung Grant S8811 from the Austrian Research Fund. The generation and characterization of the Lang-DTR-EGFP mice were supported by Association pour la Recherche sur le Cancer, Agence Nationale de la Recherche and Fondation pour la Recherche Medicale. N.R. and F.K. were supported by the Kompetenzzentrum Medizin Tirol (KMT 03b).
2 Address correspondence and reprint requests to Dr. Peter Hammerl, Department of Molecular Biology, University of Salzburg, Hellbrunner Strasse 34, 5020 Salzburg, Austria. E-mail address: peter.hammerl{at}sbg.ac.at
3 Abbreviations used in this paper: LC, Langerhans cell; 
Gal, -galactosidase; DC, dendritic cell; DT, diphtheria toxin; i.d., intradermally; LN, lymph node; EGFP, enhanced GFP; psi, pounds per square inch.
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