This Article Full Text Full Text (PDF) All Versions of this Article: 2008-0446OCv1 41/4/440    most recent Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Google Scholar Articles by Ozawa, Y. Articles by Chida, K. PubMed PubMed Citation Articles by Ozawa, Y. Articles by Chida, K.

Mucosal Vaccine Using CTL Epitope-Pulsed Dendritic Cell Confers Protection for Intracellular Pathogen

¹ Second Division, Department of Internal Medicine, ² Department of Microbiology and Immunology, and ³ Department of Clinical Pharmacology and Therapeutics, Hamamatsu University School of Medicine, Hamamatsu, Japan

Correspondence and requests for reprints should be addressed to Takafumi Suda, M.D., Ph.D., 1-20-1 Handayama, Hamamatsu, 431-3192, Japan. E-mail: suda{at}hama-med.ac.jp

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- 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.

Key Words: mucosal vaccine • Listeria monocytogenes • cytotoxic T cells • immunodominant epitope

CLINICAL RELEVANCE This study showed that intratracheal injection of single immunodominant epitope-loaded dendritic cell (DC) confers protection against respiratory infections with intracellular pathogens. Thus, mucosal vaccination using cytotoxic T cell (CTL) epitope-loaded DC is a promising strategy for generating protective CTL against intracellular pathogens in the lung.