Effect of adenovirus gene transfer vectors on the immunologic functions of mouse dendritic cells

Robert J. Korst, Ali Mahtabifard, Reiko Yamada, Ronald Crystal

Research output: Contribution to journalArticle

44 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)307-315
Number of pages9
JournalMolecular Therapy
Volume5
Issue number3
DOIs
Publication statusPublished - 1 Jan 2002
Externally publishedYes

Fingerprint

Adenoviridae
Dendritic Cells
Bone Marrow
Genes
Transgenes
T-Lymphocytes
Antigens
Hybridomas
Antigen-Presenting Cells
Intercellular Adhesion Molecule-1
Interleukin-12
Green Fluorescent Proteins
Phagocytosis
Cell Survival
Up-Regulation
Lymph Nodes
Peptides

Keywords

  • Adenovirus
  • Cellular activation
  • Dendritic cells
  • Gene therapy

ASJC Scopus subject areas

  • Molecular Medicine
  • Molecular Biology
  • Genetics
  • Pharmacology
  • Drug Discovery

Cite this

Effect of adenovirus gene transfer vectors on the immunologic functions of mouse dendritic cells. / Korst, Robert J.; Mahtabifard, Ali; Yamada, Reiko; Crystal, Ronald.

In: Molecular Therapy, Vol. 5, No. 3, 01.01.2002, p. 307-315.

Research output: Contribution to journalArticle

Korst, Robert J. ; Mahtabifard, Ali ; Yamada, Reiko ; Crystal, Ronald. / Effect of adenovirus gene transfer vectors on the immunologic functions of mouse dendritic cells. In: Molecular Therapy. 2002 ; Vol. 5, No. 3. pp. 307-315.
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