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.
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.
Enomoto
Noriyuki
N
Department of Internal Medicine, Second Division, Hamamatsu University School of Medicine, Hamamatsu, Japan.
Nagata
Toshi
T
Suda
Takafumi
T
Uchijima
Masato
M
Nakamura
Yutaro
Y
Chida
Kingo
K
Nakamura
Hirotoshi
H
Koide
Yukio
Y
D000818:Animals; D001427:Bacterial Toxins / Q000276:immunology; D016827:CD8 Antigens; D015169:Colony Count, Microbial; D003601:Cytotoxicity Tests, Immunologic; D003713:Dendritic Cells / Q000276:immunology*; D018984:Epitopes, T-Lymphocyte / Q000276:immunology; D005699:Galactosylceramides / Q000276:immunology*; D006360:Heat-Shock Proteins / Q000276:immunology; D006460:Hemolysin Proteins / Q000276:immunology; D007117:Immunization, Secondary / Q000379:methods*; D019041:L-Selectin / Q000032:analysis; D008089:Listeria monocytogenes / Q000276:immunology*; D008088:Listeriosis / Q000276:immunology / Q000517:prevention & control*; D051379:Mice; D008807:Mice, Inbred BALB C; D013154:Spleen / Q000382:microbiology; D016176:T-Lymphocyte Subsets / Q000276:immunology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D014611:Vaccination / Q000379:methods*
D001427:Bacterial Toxins; D016827:CD8 Antigens; D018984:Epitopes, T-Lymphocyte; D005699:Galactosylceramides; D006360:Heat-Shock Proteins; D006460:Hemolysin Proteins; C493154:alpha-galactosylceramide; D019041:L-Selectin; C038705:hlyA protein, Listeria monocytogenes