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Human dendritic cells very efficiently present a heterologous antigen expressed on the surface of recombinant gram-positive bacteria to CD4+ T lymphocytes.

Recombinant Streptococcus gordonii expressing on the surface the C-fragment of tetanus toxin was tested as an Ag delivery system for human monocyte-derived dendritic cells (DCs). DCs incubated with recombinant S. gordonii were much more efficient than DCs pulsed with soluble C-fragment of tetanus to... Full description

Journal Title: Journal of immunology (Baltimore Md. : 1950), September 15, 1999, Vol.163(6), pp.3029-3036
Main Author: Corinti, S
Other Authors: Medaglini, D , Cavani, A , Rescigno, M , Pozzi, G , Ricciardi-Castagnoli, P , Girolomoni, G
Format: Electronic Article Electronic Article
Language: English
Subjects:
ID: ISSN: 0022-1767
Link: http://search.proquest.com/docview/70021155/?pq-origsite=primo
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title: Human dendritic cells very efficiently present a heterologous antigen expressed on the surface of recombinant gram-positive bacteria to CD4+ T lymphocytes.
format: Article
creator:
  • Corinti, S
  • Medaglini, D
  • Cavani, A
  • Rescigno, M
  • Pozzi, G
  • Ricciardi-Castagnoli, P
  • Girolomoni, G
subjects:
  • Antigen Presentation–Biosynthesis
  • Antigens, Bacterial–Immunology
  • Cd4-Positive T-Lymphocytes–Metabolism
  • Cell Differentiation–Immunology
  • Chemokines–Metabolism
  • Clone Cells–Microbiology
  • Cytokines–Immunology
  • Dendritic Cells–Metabolism
  • Endocytosis–Metabolism
  • Epitopes, T-Lymphocyte–Immunology
  • Humans–Metabolism
  • Peptide Fragments–Microbiology
  • Phagocytosis–Immunology
  • Recombinant Fusion Proteins–Metabolism
  • Streptococcus–Immunology
  • Tetanus Toxin–Metabolism
  • Tetanus Toxin–Immunology
  • Tetanus Toxin–Biosynthesis
  • Tetanus Toxin–Genetics
  • Tetanus Toxin–Genetics
  • Tetanus Toxin–Immunology
  • Tetanus Toxin–Metabolism
  • Tetanus Toxin–Immunology
  • Tetanus Toxin–Metabolism
  • Abridged
  • Antigens, Bacterial
  • Chemokines
  • Cytokines
  • Epitopes, T-Lymphocyte
  • Peptide Fragments
  • Recombinant Fusion Proteins
  • Tetanus Toxin
  • Tetanus Toxin Fragment C
ispartof: Journal of immunology (Baltimore, Md. : 1950), September 15, 1999, Vol.163(6), pp.3029-3036
description: Recombinant Streptococcus gordonii expressing on the surface the C-fragment of tetanus toxin was tested as an Ag delivery system for human monocyte-derived dendritic cells (DCs). DCs incubated with recombinant S. gordonii were much more efficient than DCs pulsed with soluble C-fragment of tetanus toxin at stimulating specific CD4 super(+) T cells as determined by cell proliferation and IFN- gamma release. Compared with DCs treated with soluble Ag, DCs fed with recombinant bacteria required 10 super(2)- to 10 super(3)-fold less Ag and were at least 10 super(2) times more effective on a per-cell basis for activating specific T cells. S. gordonii was internalized in DCs by conventional phagocytosis, and cytochalasin D inhibited presentation of bacteria-associated Ag, but not of soluble Ag, suggesting that phagocytosis was required for proper delivery of recombinant Ag. Bacteria were also very potent inducers of DC maturation, although they enhanced the capacity of DCs to activate specific CD4 super(+) T cells at concentrations that did not stimulate DC maturation. In particular, S. gordonii dose-dependently up-regulated expression of membrane molecules (MHC I and II, CD80, CD86, CD54, CD40, CD83) and reduced both phagocytic and endocytic activities. Furthermore, bacteria promoted in a dose-dependent manner DC release of cytokines (IL-6, TNF- alpha , IL-1 beta , IL-12, TGF- beta , and IL-10) and of the chemokines IL-8, RANTES, IFN- gamma -inducible protein-10, and monokine induced by IFN- gamma . Thus, recombinant Gram-positive bacteria appear a powerful tool for vaccine design due to their extremely high capacity to deliver Ags into DCs, as well as induce DC maturation and secretion of T cell chemoattractans.
language: eng
source:
identifier: ISSN: 0022-1767
fulltext: fulltext
issn:
  • 00221767
  • 0022-1767
url: Link


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titleHuman dendritic cells very efficiently present a heterologous antigen expressed on the surface of recombinant gram-positive bacteria to CD4+ T lymphocytes.
creatorCorinti, S ; Medaglini, D ; Cavani, A ; Rescigno, M ; Pozzi, G ; Ricciardi-Castagnoli, P ; Girolomoni, G
contributorCorinti, S (correspondence author) ; Corinti, S (record owner)
ispartofJournal of immunology (Baltimore, Md. : 1950), September 15, 1999, Vol.163(6), pp.3029-3036
identifierISSN: 0022-1767
subjectAntigen Presentation–Biosynthesis ; Antigens, Bacterial–Immunology ; Cd4-Positive T-Lymphocytes–Metabolism ; Cell Differentiation–Immunology ; Chemokines–Metabolism ; Clone Cells–Microbiology ; Cytokines–Immunology ; Dendritic Cells–Metabolism ; Endocytosis–Metabolism ; Epitopes, T-Lymphocyte–Immunology ; Humans–Metabolism ; Peptide Fragments–Microbiology ; Phagocytosis–Immunology ; Recombinant Fusion Proteins–Metabolism ; Streptococcus–Immunology ; Tetanus Toxin–Metabolism ; Tetanus Toxin–Immunology ; Tetanus Toxin–Biosynthesis ; Tetanus Toxin–Genetics ; Tetanus Toxin–Genetics ; Tetanus Toxin–Immunology ; Tetanus Toxin–Metabolism ; Tetanus Toxin–Immunology ; Tetanus Toxin–Metabolism ; Abridged ; Antigens, Bacterial ; Chemokines ; Cytokines ; Epitopes, T-Lymphocyte ; Peptide Fragments ; Recombinant Fusion Proteins ; Tetanus Toxin ; Tetanus Toxin Fragment C
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descriptionRecombinant Streptococcus gordonii expressing on the surface the C-fragment of tetanus toxin was tested as an Ag delivery system for human monocyte-derived dendritic cells (DCs). DCs incubated with recombinant S. gordonii were much more efficient than DCs pulsed with soluble C-fragment of tetanus toxin at stimulating specific CD4 super(+) T cells as determined by cell proliferation and IFN- gamma release. Compared with DCs treated with soluble Ag, DCs fed with recombinant bacteria required 10 super(2)- to 10 super(3)-fold less Ag and were at least 10 super(2) times more effective on a per-cell basis for activating specific T cells. S. gordonii was internalized in DCs by conventional phagocytosis, and cytochalasin D inhibited presentation of bacteria-associated Ag, but not of soluble Ag, suggesting that phagocytosis was required for proper delivery of recombinant Ag. Bacteria were also very potent inducers of DC maturation, although they enhanced the capacity of DCs to activate specific CD4 super(+) T cells at concentrations that did not stimulate DC maturation. In particular, S. gordonii dose-dependently up-regulated expression of membrane molecules (MHC I and II, CD80, CD86, CD54, CD40, CD83) and reduced both phagocytic and endocytic activities. Furthermore, bacteria promoted in a dose-dependent manner DC release of cytokines (IL-6, TNF- alpha , IL-1 beta , IL-12, TGF- beta , and IL-10) and of the chemokines IL-8, RANTES, IFN- gamma -inducible protein-10, and monokine induced by IFN- gamma . Thus, recombinant Gram-positive bacteria appear a powerful tool for vaccine design due to their extremely high capacity to deliver Ags into DCs, as well as induce DC maturation and secretion of T cell chemoattractans.
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titleHuman dendritic cells very efficiently present a heterologous antigen expressed on the surface of recombinant gram-positive bacteria to CD4+ T lymphocytes.
authorCorinti, S ; Medaglini, D ; Cavani, A ; Rescigno, M ; Pozzi, G ; Ricciardi-Castagnoli, P ; Girolomoni, G
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