Abstract
Dendritic cells (DCs) are potent APCs for naive CD8(+) T cells and are being investigated as vaccine delivery vehicles. In this study, we examine the CD8(+) T cell response to defined peptides from Listeria monocytogenes (LM), lymphocytic choriomeningitis virus, and murine CMV coated singly and in combination onto mature bone marrow-derived DCs (BMDCs). We show that immunization of mice with 2 x 10(5) mature BMDCs coated with multiple MHC class I peptides generates a significant Ag-specific CD8(+) T cell response in both the spleen and nonlymphoid organs. This immunization resulted in a peptide-specific hierarchy in the magnitude of CD8(+) T cell priming and noncoordinate kinetics in response to different peptide epitopes. Kinetics were not exclusively due to specific characteristics of the MHC class I molecule, and were not altered in an Ag-independent manner by concurrent LM infection. Mice immunized with listeriolysin O 91-99-coated BMDCs are protected against high dose challenge with virulent LM. This protection was enhanced by diversifying the memory CD8(+) T cell compartment, even in the absence of a large increase in Ag-specific CD8(+) memory T cells.
Publication types
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Animals
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Antigen Presentation
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Bacterial Proteins / administration & dosage
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Bacterial Proteins / immunology
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Bacterial Proteins / metabolism
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Bacterial Toxins*
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Bone Marrow Cells / immunology
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Bone Marrow Cells / microbiology
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Bone Marrow Transplantation
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CD8-Positive T-Lymphocytes / cytology*
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CD8-Positive T-Lymphocytes / immunology*
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CD8-Positive T-Lymphocytes / microbiology
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Cell Division / immunology
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Dendritic Cells / immunology
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Dendritic Cells / microbiology
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Dendritic Cells / transplantation*
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Epitopes, T-Lymphocyte / analysis
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Epitopes, T-Lymphocyte / immunology
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Female
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H-2 Antigens / immunology
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H-2 Antigens / metabolism
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Heat-Shock Proteins / administration & dosage
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Heat-Shock Proteins / immunology
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Heat-Shock Proteins / metabolism
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Hemolysin Proteins
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Histocompatibility Antigen H-2D
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Immunity, Innate
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Immunologic Memory*
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Injections, Intravenous
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Kinetics
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Listeriosis / immunology
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Listeriosis / prevention & control
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Liver / cytology
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Liver / immunology
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Liver / microbiology
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Lung / cytology
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Lung / immunology
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Lung / microbiology
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Lymphocyte Activation*
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Lymphocyte Count
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Mice
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Mice, Inbred BALB C
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Oligopeptides / administration & dosage
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Oligopeptides / immunology*
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Oligopeptides / metabolism
Substances
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Bacterial Proteins
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Bacterial Toxins
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Epitopes, T-Lymphocyte
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H-2 Antigens
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H-2K(K) antigen
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Heat-Shock Proteins
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Hemolysin Proteins
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Histocompatibility Antigen H-2D
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Oligopeptides
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hlyA protein, Listeria monocytogenes