Antigen-pulsed dendritic cells expressing macrophage-derived chemokine elicit Th2 responses and promote specific humoral immunity. Academic Article uri icon

Overview

MeSH

  • Adenoviridae
  • Animals
  • Antibodies, Bacterial
  • Antibody Specificity
  • Antigen Presentation
  • Antigens, Bacterial
  • Chemokine CCL22
  • Female
  • Gene Expression
  • Immunization
  • Immunization, Passive
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred C57BL
  • Mice, Mutant Strains
  • Pseudomonas Infections
  • Pseudomonas aeruginosa
  • Transduction, Genetic

MeSH Major

  • Chemokines, CC
  • Dendritic Cells
  • Macrophages
  • Th2 Cells

abstract

  • Macrophage-derived chemokine (MDC) is a potent chemoattractant for antigen-specific T lymphocytes. We hypothesized that Adenovirus- (Ad-) transduced dendritic cells (DCs) overexpressing MDC would enhance the T cell-mediated humoral immune response specific for antigens presented by the DC. We challenged two strains of mice with lethal Pseudomonas aeruginosa infection 3 weeks after immunization with AdMDC-modified DCs pulsed with heat-killed P. aeruginosa. MDC-expressing DCs specifically attracted T lymphocytes and preserved typical DC surface phenotypes without growth factors in vitro. Mice immunized with AdMDC/Pseudomonas/DCs developed high levels of serum anti-Pseudomonas Ab's and were protected from a lethal respiratory challenge with Pseudomonas. The in vivo protective immunity required CD4(+) T cells, B cells, and IL-4, but not CD8(+) T cells and IL-12. AdMDC/DCs pulsed with Pseudomonas yielded significant but not absolute cross-protection against different strains of P. aeruginosa. Pseudomonas-pulsed AdMDC/DCs protected mice from Pseudomonas but not Escherichia coli and vice versa; this microbe-specific protection correlated with microbe-specific induction of CD4(+) T cell proliferation and IL-4 secretion. Based on these observations, AdMDC-modified DCs pulsed with a killed bacteria may be a useful approach to vaccination against infectious disorders.

publication date

  • September 2001

has subject area

  • Adenoviridae
  • Animals
  • Antibodies, Bacterial
  • Antibody Specificity
  • Antigen Presentation
  • Antigens, Bacterial
  • Chemokine CCL22
  • Chemokines, CC
  • Dendritic Cells
  • Female
  • Gene Expression
  • Immunization
  • Immunization, Passive
  • Macrophages
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred C57BL
  • Mice, Mutant Strains
  • Pseudomonas Infections
  • Pseudomonas aeruginosa
  • Th2 Cells
  • Transduction, Genetic

Research

keywords

  • Journal Article

Identity

Language

  • eng

PubMed Central ID

  • PMC200925

Digital Object Identifier (DOI)

  • 10.1172/JCI11564

PubMed ID

  • 11560961

Additional Document Info

start page

  • 917

end page

  • 927

volume

  • 108

number

  • 6