Abstract
Cytotoxic T lymphocytes (CTL) respond to antigenic peptides presented on MHC class I molecules. On most cells, these peptides are exclusively of endogenous, cytosolic origin. Bone marrow-derived antigen-presenting cells, however, harbor a unique pathway for MHC I presentation of exogenous antigens. This mechanism permits cross-presentation of pathogen-infected cells and the priming of CTL responses against intracellular microbial infections. Here, we report a novel diphtheria toxin-based system that allows the inducible, short-term ablation of dendritic cells (DC) in vivo. We show that in vivo DC are required to cross-prime CTL precursors. Our results thus define a unique in vivo role of DC, i.e., the sensitization of the immune system for cell-associated antigens. DC-depleted mice fail to mount CTL responses to infection with the intracellular bacterium Listeria monocytogenes and the rodent malaria parasite Plasmodium yoelii.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Animals
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CD8-Positive T-Lymphocytes / immunology*
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Dendritic Cells / immunology*
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Diphtheria Toxin / immunology
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Heparin-binding EGF-like Growth Factor
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Integrin alphaXbeta2 / genetics
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Integrin alphaXbeta2 / immunology*
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Intercellular Signaling Peptides and Proteins
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Listeria monocytogenes / immunology
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Liver / parasitology
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Mice
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Mice, Inbred BALB C
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Mice, Inbred C57BL
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Mice, Transgenic
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Models, Animal
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Plasmodium yoelii / immunology
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Plasmodium yoelii / physiology
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Receptors, Cell Surface / genetics
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Receptors, Cell Surface / immunology
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Recombinant Fusion Proteins / genetics
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Recombinant Fusion Proteins / immunology
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T-Lymphocytes, Cytotoxic / immunology
Substances
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Diphtheria Toxin
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Hbegf protein, mouse
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Heparin-binding EGF-like Growth Factor
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Integrin alphaXbeta2
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Intercellular Signaling Peptides and Proteins
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Receptors, Cell Surface
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Recombinant Fusion Proteins