Abstract
Neutrophils modulated Ag presentation following immunization with Ags in CFA or IFA or alum. The neutrophils had an important negative role in the CD4 T cell and B cell responses to three protein Ags: hen egg white lysozyme, OVA, and listeriolysin O. In their absence (by depleting with Abs for only the first 24 h, or using genetically neutropenic mice), the cellular responses increased several-fold. The CD8 response was not affected or slightly decreased. Competition for Ag between the presenting cells and the neutrophils, as well as an effect on the response to Ag-bearing dendritic cells (DCs), was documented. Neutrophils entered the draining lymph nodes rapidly and for a brief period of several hours, localizing mainly to the marginal sinus and superficial cortex. There they established brief contact with DCs and macrophages. Moreover, neutrophils imprinted on the quality of the subsequent DC-T cell interactions, despite no physical contact with them; by intravital microscopy, the clustering of Ag-specific T cells and DCs was improved in neutropenic mice. Thus, neutrophils are obligate cells that briefly enter sites of immunization and set the level of Ag presentation. A brief depletion may have a considerably positive impact on vaccination.
Publication types
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Comparative Study
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Research Support, N.I.H., Extramural
MeSH terms
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Adjuvants, Immunologic / administration & dosage*
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Adjuvants, Immunologic / physiology
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Alum Compounds / administration & dosage*
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Amino Acid Sequence
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Animals
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Antigen Presentation / genetics
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Antigen Presentation / immunology*
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B-Lymphocytes / immunology
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B-Lymphocytes / metabolism
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Bacterial Toxins / administration & dosage
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Bacterial Toxins / immunology
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Bacterial Toxins / metabolism
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Cell Movement / genetics
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Cell Movement / immunology
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Freund's Adjuvant / administration & dosage*
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Freund's Adjuvant / immunology
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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 / administration & dosage
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Hemolysin Proteins / immunology
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Hemolysin Proteins / metabolism
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Lipids / administration & dosage*
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Lipids / immunology
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Lymph Nodes / immunology
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Lymph Nodes / metabolism
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Lymph Nodes / pathology
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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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Molecular Sequence Data
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Muramidase / administration & dosage
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Muramidase / immunology*
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Muramidase / metabolism
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Neutrophils / immunology*
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Neutrophils / metabolism*
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Neutrophils / pathology
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T-Lymphocytes / immunology
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T-Lymphocytes / metabolism
Substances
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Adjuvants, Immunologic
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Alum Compounds
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Bacterial Toxins
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Heat-Shock Proteins
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Hemolysin Proteins
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Lipids
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incomplete Freund's adjuvant
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aluminum sulfate
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Freund's Adjuvant
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hen egg lysozyme
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Muramidase
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hlyA protein, Listeria monocytogenes