title: Epidermal langerhans cells are dispensable for humoral and cell-mediated immunity elicited by gene gun immunization.
abstract: 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-gamma 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.
authors.affiliation: Christian Doppler Laboratory of Allergy Diagnostics and Therapy, Department of Molecular Biology, University Salzburg, Salzburg, Austria.
authors.forename: Angelika
authors.initials: A
authors.lastname: Stoecklinger
authors.forename: Ines
authors.initials: I
authors.lastname: Grieshuber
authors.forename: Sandra
authors.initials: S
authors.lastname: Scheiblhofer
authors.forename: Richard
authors.initials: R
authors.lastname: Weiss
authors.forename: Uwe
authors.initials: U
authors.lastname: Ritter
authors.forename: Adrien
authors.initials: A
authors.lastname: Kissenpfennig
authors.forename: Bernard
authors.initials: B
authors.lastname: Malissen
authors.forename: Nikolaus
authors.initials: N
authors.lastname: Romani
authors.forename: Franz
authors.initials: F
authors.lastname: Koch
authors.forename: Fatima
authors.initials: F
authors.lastname: Ferreira
authors.forename: Josef
authors.initials: J
authors.lastname: Thalhamer
authors.forename: Peter
authors.initials: P
authors.lastname: Hammerl
mesh_terms: D000818:Animals; D000917:Antibody Formation / Q000276:immunology; D019470:Biolistics; D019496:Cancer Vaccines / Q000008:administration & dosage; D049109:Cell Proliferation; D000078404:Epidermal Cells; D004817:Epidermis / Q000276:immunology*; D005434:Flow Cytometry; D066257:Heparin-binding EGF-like Growth Factor; D006801:Humans; D007111:Immunity, Cellular; D007114:Immunization / Q000379:methods*; D007150:Immunohistochemistry; D036341:Intercellular Signaling Peptides and Proteins; D007371:Interferon-gamma / Q000378:metabolism; D007801:Langerhans Cells / Q000276:immunology*; D008213:Lymphocyte Activation / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009374:Neoplasms, Experimental / Q000276:immunology / Q000517:prevention & control; D011956:Receptors, Cell Surface / Q000235:genetics / Q000276:immunology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013601:T-Lymphocytes / Q000276:immunology; D019444:Vaccines, DNA / Q000008:administration & dosage
chemical_list: D019496:Cancer Vaccines; C587883:HBEGF protein, human; C587884:Hbegf protein, mouse; D066257:Heparin-binding EGF-like Growth Factor; D036341:Intercellular Signaling Peptides and Proteins; D011956:Receptors, Cell Surface; D019444:Vaccines, DNA; D007371:Interferon-gamma