Immunization with dendritic cells loaded with alpha-galactosylceramide at priming phase, but not at boosting phase, enhances cytotoxic T lymphocyte activity against infection by intracellular bacteria.

Abstract

We evaluated the effect of immunization with dendritic cells (DCs) pulsed with alpha-galactosylceramide (alphaGalCer) and listeriolysin O (LLO) 91-99 peptide, a dominant cytotoxic T lymphocyte (CTL) epitope of Listeria monocytogenes by observing the responses of specific CD8(+) T cells and in vivo CTL activity. DCs were pulsed with various combinations of alphaGalCer and LLO91-99 peptide and administered to BALB/c mice. Immunization with DCs pulsed with alphaGalCer and LLO91-99 at priming phase and with DCs pulsed with LLO91-99 alone at boosting phase induced stronger in vivo CTL activity, reduced the bacterial load in spleens of Listeria-challenged mice and augmented CD62L(+) CD8(+) central memory T cells compared with other immunization protocols. The blockade of interferon-gamma (IFN-gamma) at boosting phase reversed the induction of CD8(+) central memory T cells and reduced the bacterial load in spleens of Listeria-challenged mice immunized with DCs pulsed with alphaGalCer and LLO91-99 at both phases, suggesting that alphaGalCer at boosting phase has deleterious effects through IFN-gamma production. These results indicate that immunization with DCs pulsed with CTL epitope peptide together with alphaGalCer at priming phase, but not at boosting phase, is feasible for eliciting a specific CTL activity and protective immunity against infection of intracellular bacteria.

• Authors: Noriyuki Enomoto, Toshi Nagata, Takafumi Suda, Masato Uchijima, Yutaro Nakamura, Kingo Chida, Hirotoshi Nakamura, Yukio Koide
• Journal: FEMS immunology and medical microbiology (FEMS Immunol Med Microbiol) Vol. 51 Issue 2 Pg. 350-62 (Nov 2007) ISSN: 0928-8244 [Print] England
• PMID: 17760876 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Bacterial Toxins
• CD8 Antigens
• Epitopes, T-Lymphocyte
• Galactosylceramides
• Heat-Shock Proteins
• Hemolysin Proteins
• alpha-galactosylceramide
• L-Selectin
• hlyA protein, Listeria monocytogenes

Topics

• Animals
• Bacterial Toxins (immunology)
• CD8 Antigens
• Colony Count, Microbial
• Cytotoxicity Tests, Immunologic
• Dendritic Cells (immunology)
• Epitopes, T-Lymphocyte (immunology)
• Galactosylceramides (immunology)
• Heat-Shock Proteins (immunology)
• Hemolysin Proteins (immunology)
• Immunization, Secondary (methods)
• L-Selectin (analysis)
• Listeria monocytogenes (immunology)
• Listeriosis (immunology, prevention & control)
• Mice
• Mice, Inbred BALB C
• Spleen (microbiology)
• T-Lymphocyte Subsets (immunology)
• T-Lymphocytes, Cytotoxic (immunology)
• Vaccination (methods)