Effect of adenovirus gene transfer vectors on the immunologic functions of mouse dendritic cells. Academic Article uri icon

Overview

MeSH

  • Animals
  • Antigen Presentation
  • Cell Movement
  • Cells, Cultured
  • Gene Expression Regulation
  • Mice
  • Phagocytosis

MeSH Major

  • Adenoviridae
  • Dendritic Cells
  • Genetic Vectors
  • Transgenes

abstract

  • To address the effect of adenovirus (Ad) gene transfer vector transduction on the diverse functions of dendritic cells, we used an Ad vector encoding no transgene (AdNull) to transduce mouse bone-marrow-derived dendritic cells (BMDC). Initial experiments using an Ad vector encoding a marker gene (AdGFP, jellyfish green fluorescent protein) showed that the optimal ratio of infectious Ad particles to each cell was 100, when both transgene expression and resultant BMDC viability were taken into account. Exposure to AdNull resulted in upregulation of both surface activation markers (CD40, MHC class II, B7.1, B7.2, ICAM-1) and IL-12 expression by BMDC. AdNull activation of BMDC was observed in multiple strains of mice. Despite this, AdNull-transduced BMDC displayed only modestly impaired antigen uptake ability, as demonstrated in macropinocytosis and phagocytosis assays, in vitro. However, Ad-modified BMDC migrated to regional lymph nodes five times more efficiently than sham-transduced BMDC in vivo. In addition, Ad transduction significantly enhanced the ability of BMDC to present a model peptide antigen to T-lymphocyte hybridoma cells at low BMDC:T cell ratios. We conclude that Ad modification, in and of itself, induces a state of activation in mouse BMDC. This activation, albeit mild compared with that induced by other stimuli, produces measurable effects of the specific immunological functions of these antigen-presenting cells.

publication date

  • March 2002

has subject area

  • Adenoviridae
  • Animals
  • Antigen Presentation
  • Cell Movement
  • Cells, Cultured
  • Dendritic Cells
  • Gene Expression Regulation
  • Genetic Vectors
  • Mice
  • Phagocytosis
  • Transgenes

Research

keywords

  • Journal Article

Identity

Language

  • eng

Digital Object Identifier (DOI)

  • 10.1006/mthe.2002.0538

PubMed ID

  • 11863421

Additional Document Info

start page

  • 307

end page

  • 315

volume

  • 5

number

  • 3