Abstract
The nature of dendritic cell(s) (DC[s]) that conditions efficient in vivo priming of CD8+ CTL after immunization via epithelial tissues remains largely unknown. Here, we show that myeloid DCs rapidly recruited by adjuvants into the buccal mucosa or skin are essential for CD8+ T cell crosspriming. Recruitment of circulating DC precursors, including Gr1+ monocytes, precedes the sequential accumulation of CD11c+ MHC class II+ DCs in dermis and epithelium via a CCR6/CCL20-dependent mechanism. Remarkably, a defect in CCR6, local neutralization of CCL20, or depletion of monocytes prevents in vivo priming of CD8+ CTL against an innocuous protein antigen administered with adjuvant. In addition, transfer of CCR6-sufficient Gr1+ monocytes restores CD8+ T cell priming in CCR6( degrees / degrees ) mice via a direct Ag presentation mechanism. Thus, newly recruited DCs likely derived from circulating monocytes are responsible for efficient crosspriming of CD8+ CTL after mucosal or skin immunization.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Adjuvants, Immunologic
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Animals
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CD8-Positive T-Lymphocytes / immunology*
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Cell Movement
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Chemokine CCL20
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Chemokines, CC / metabolism
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Chemokines, CC / physiology*
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Clodronic Acid / pharmacology
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Dendritic Cells / immunology*
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Dermis / metabolism
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Dinitrofluorobenzene / pharmacology
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Epithelium / immunology
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Epithelium / metabolism
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Female
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H-2 Antigens / genetics
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H-2 Antigens / physiology
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Immunization
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Langerhans Cells / physiology
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Macrophage Inflammatory Proteins / metabolism
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Macrophage Inflammatory Proteins / physiology*
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Mice
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Mice, Inbred C57BL
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Mice, Knockout
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Mice, Transgenic
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Mouth Mucosa / cytology
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Mouth Mucosa / immunology
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Mouth Mucosa / metabolism
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Nucleoproteins / immunology
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Receptors, CCR6
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Receptors, Chemokine / genetics
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Receptors, Chemokine / physiology*
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Stem Cells / physiology
Substances
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Adjuvants, Immunologic
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CCL20 protein, human
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CCR6 protein, human
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Chemokine CCL20
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Chemokines, CC
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H-2 Antigens
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Macrophage Inflammatory Proteins
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Nucleoproteins
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Receptors, CCR6
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Receptors, Chemokine
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Clodronic Acid
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Dinitrofluorobenzene