title: Mucosal vaccine using CTL epitope-pulsed dendritic cell confers protection for intracellular pathogen.
abstract: Effective protective immunity against respiratory infections with intracellular pathogens requires pathogen-specific cytotoxic T cells (CTL) in the lung. However, vaccines that induce pathogen-specific CTL in the lung are poorly explored. Dendritic cells (DC) have increasingly been exploited as vaccines against infections. However, few studies have investigated the ability of mucosal DC vaccines to elicit protective CTL responses in the lung. Our objective was to develop an efficacious mucosal DC vaccine to generate protective CTL against respiratory infections with intracellular pathogens. Bone marrow-derived DC (BM-DC) pulsed with a single immunodominant CTL epitope, listeriolysin O (LLO) 91-99, of Listeria monocytogenes (LM) were intratracheally administered into mice. The frequency and function of epitope-specific CTL in mediastinal lymph nodes (MLN) and spleen were assessed for their ability to protect against LM infection. After intratracheal administration, lipopolysaccharide (LPS)-treated LLO 91-99-loaded BM-DC (LPS-LLO DC) more frequently migrated to MLN than LPS-untreated LLO 91-99-loaded BM-DC (LLO DC). Using tetrameric H2-K(d)/LLO 91-99 peptide complex, specific CD8(+) T cells were found in MLN as well as the spleen in LPS-LLO DC-immunized mice, but not in LLO-DC-immunized mice. Both MLN and spleen cells obtained from LPS-LLO DC-immunized mice produced large amounts of IFN-gamma in response to LLO 91-99 with high epitope-specific CTL activities. Vaccination with LPS-LLO DC, but not LLO DC, protected mice against lethal respiratory infection with LM. These data suggest that mucosal vaccination with LPS-treated immunodominant CTL epitope-loaded DC is a promising strategy for generating protective CTL against respiratory infections with intracellular pathogens.
authors.affiliation: Department of Internal Medicine, Hamamatsu University School of Medicine, Hamamatsu, Japan.
authors.forename: Yuichi
authors.initials: Y
authors.lastname: Ozawa
authors.forename: Takafumi
authors.initials: T
authors.lastname: Suda
authors.forename: Toshi
authors.initials: T
authors.lastname: Nagata
authors.forename: Dai
authors.initials: D
authors.lastname: Hashimoto
authors.forename: Yutaro
authors.initials: Y
authors.lastname: Nakamura
authors.forename: Noriyuki
authors.initials: N
authors.lastname: Enomoto
authors.forename: Naoki
authors.initials: N
authors.lastname: Inui
authors.forename: Yukio
authors.initials: Y
authors.lastname: Koide
authors.forename: Hirotoshi
authors.initials: H
authors.lastname: Nakamura
authors.forename: Kingo
authors.initials: K
authors.lastname: Chida
mesh_terms: D000280:Administration, Inhalation; D000818:Animals; D001427:Bacterial Toxins / Q000276:immunology*; D001428:Bacterial Vaccines / Q000008:administration & dosage / Q000276:immunology*; D002465:Cell Movement; D003713:Dendritic Cells / Q000276:immunology*; D004353:Drug Evaluation, Preclinical; D006360:Heat-Shock Proteins / Q000276:immunology*; D006460:Hemolysin Proteins / Q000276:immunology*; D007114:Immunization; D016056:Immunodominant Epitopes / Q000276:immunology*; D007371:Interferon-gamma / Q000096:biosynthesis; D008089:Listeria monocytogenes / Q000276:immunology*; D008088:Listeriosis / Q000517:prevention & control; D008168:Lung / Q000473:pathology; D008198:Lymph Nodes / Q000276:immunology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D009092:Mucous Membrane / Q000276:immunology; D010446:Peptide Fragments / Q000276:immunology; D018410:Pneumonia, Bacterial / Q000517:prevention & control; D054400:Receptors, CCR7 / Q000096:biosynthesis; D013154:Spleen / Q000276:immunology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D014132:Trachea / Q000276:immunology
chemical_list: D001427:Bacterial Toxins; D001428:Bacterial Vaccines; C515371:Ccr7 protein, mouse; D006360:Heat-Shock Proteins; D006460:Hemolysin Proteins; D016056:Immunodominant Epitopes; D010446:Peptide Fragments; D054400:Receptors, CCR7; D007371:Interferon-gamma; C038705:hlyA protein, Listeria monocytogenes