Potent maturation of monocyte-derived dendritic cells after cd40l lentiviral gene delivery

Richard C. Koya, Nori Kasahara, Patricia M.B. Favaro, Roy Lau, Huy Q. Ta, Jeffrey S. Weber, Renata Stripecke

Research output: Contribution to journalArticlepeer-review

48 Scopus citations

Abstract

Dendritic cells (DCs) are being evaluated in immunization protocols to enhance immunity against infectious diseases and cancer. Interaction of T-helper cells expressing CD40 ligand (CD40L) with its cognate CD40 receptor on DCs leads to a mature DC phenotype, characterized by increased capacity of antigen presentation to cytotoxic T cells. The authors examined the ability of third-generation self-inactivating lentiviral vectors expressing CD40L to induce autonomous maturation of ex vivo expanded human monocyte-derived dendritic cells. Transduction with lentiviral vectors achieved a highly efficient gene transfer of CD40L to DCs, which correlated with phenotypic maturation as shown by the expression of immunologic relevant markers (CD83, CD80, MHCI) and secretion of IL-12, whereas DC phenotype was not affected by a control vector expressing only the green fluorescent protein marker. Addition of recombinant IFN-γ to DCs at the time of CD40L transduction further enhanced IL-12 production, and when co-cultured with allogeneic and autologous CD8+ and CD4+ T cells, a potent activation was observed. Autologous responses against an HLA-A2-restricted influenza peptide (Flu-M1) and a tumor-associated antigenic peptide (gp100 210M) were significantly enhanced when CD40L transduced DCs were used as antigen-presenting cells for in vitro stimulation of CD8+ cytotoxic T lymphocytes. These results demonstrate that endogenous expression of CD40L by lentivirally transduced DCs induced their autonomous maturation to a phenotype comparable to that induced by optimal concentrations of soluble CD40L, providing a novel tool for genetic manipulation of DCs.

Original languageEnglish (US)
Pages (from-to)451-460
Number of pages10
JournalJournal of Immunotherapy
Volume26
Issue number5
DOIs
StatePublished - 2003
Externally publishedYes

Keywords

  • CD40L
  • Dendritic cells
  • Gene therapy
  • Immunotherapy
  • Lentiviral vectors
  • Melanoma

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Pharmacology
  • Cancer Research

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