Abstract
Dendritic cells (DC) are potent APCs for naive T cells in vivo. This is evident by inducing T cell responses through adoptive DC transfer. Priming specific CTL responses in vivo often requires "help". We study alternative sources of help in DC-dependent priming of MHC class I-restricted CTL. Priming an anti-viral CTL response in naive B6 mice by adoptive transfer of antigenic peptide-pulsed DC required CD4(+) T cell help. CTL priming was facilitated by providing MHC class II-dependent specific help. Furthermore, transfers of MHC class II-deficient pulsed DC into naive, normal hosts, or DC transfers into naive, CD4(+) T cell-depleted hosts primed CTL inefficiently. Pretreatment of DC with immune-stimulating oligodeoxynucleotides rendered them more efficient for CD4(+) T cell-independent priming of CTL. DC copresenting a K(b)-binding antigenic peptide and the CD1d-binding glycolipid alpha-galactosyl-ceramide efficiently primed CTL in a class II-independent way. To obtain NKT cell-dependent help in CTL priming, the same DC had to present both the peptide and the glycolipid. CTL priming by adoptive DC transfer was largely NK cell-dependent. The requirement for NK cells was only partially overcome by recruiting NKT cell help into DC-dependent CTL priming. NKT cells thus are potent helper cells for DC-dependent CTL priming.
Publication types
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Comparative Study
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Research Support, Non-U.S. Gov't
MeSH terms
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Adoptive Transfer
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Amino Acid Sequence
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Animals
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Antigens, CD1 / biosynthesis
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Antigens, CD1 / genetics
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Antigens, CD1 / physiology
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Antigens, CD1d
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Bone Marrow Cells / immunology
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Bone Marrow Cells / metabolism
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Bone Marrow Transplantation
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CD4-Positive T-Lymphocytes / immunology
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CD4-Positive T-Lymphocytes / metabolism
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CD8-Positive T-Lymphocytes / immunology*
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CD8-Positive T-Lymphocytes / metabolism
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Cells, Cultured
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Ceramides / immunology
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Ceramides / metabolism
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Cytotoxicity, Immunologic* / genetics
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Dendritic Cells / immunology*
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Dendritic Cells / metabolism
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Dendritic Cells / transplantation
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Female
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H-2 Antigens / immunology*
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Histocompatibility Antigens Class II / genetics
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Histocompatibility Antigens Class II / physiology
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Immunization
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Killer Cells, Natural / immunology*
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Killer Cells, Natural / metabolism
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Lymphocyte Activation / genetics
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Lymphocyte Cooperation / genetics
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Lymphocyte Cooperation / immunology*
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Male
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Mice
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Mice, Inbred C57BL
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Mice, Knockout
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Molecular Sequence Data
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T-Lymphocyte Subsets / immunology*
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T-Lymphocyte Subsets / metabolism
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T-Lymphocytes, Cytotoxic / immunology
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T-Lymphocytes, Cytotoxic / metabolism
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Tumor Cells, Cultured
Substances
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AGL 563
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Antigens, CD1
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Antigens, CD1d
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Ceramides
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H-2 Antigens
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H-2Kb protein, mouse
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Histocompatibility Antigens Class II