Transgenic interleukin 2 secreted by CML dendritic cells stimulates autologous TH1 T cells

A. B. Dietz, M. R. Litzow, P. A. Bulur, S. Vuk-Pavlović

Research output: Contribution to journalArticle

6 Scopus citations

Abstract

Background: We investigated if dendritic cells (DC), derived from patients suffering from chronic myeloid leukemia (CML) could be modified by recombinant replication-defective adenoviruses to express functional interleukin 2 (IL-2). Such modification might confer onto antigen-presenting cells the ability to stimulate expansion of effector cells. Methods: To quantify the infection efficiency of CML dendritic cells (CML-DC) by recombinant adenovirus, we measured the expression of green fluorescent protein (GFP) gene contained in the virus. In CML-DC infected with an adenovirus containing the IL-2 gene, we evaluated their ability to secrete IL-2 and stimulate proliferation of autologous T cells. Results: Uninfected CML-DC and normal DC secreted similar amounts of IL-12 and stimulated similarly efficient autologous mixed leukocyte reaction. Immature CML-DC infected by an adenovirus containing the gene for IL-2 secreted large amounts of IL-2 and stimulated proliferation of autologous T cells more efficiently than the corresponding CML-DC alone. High levels of interferon η, but not of IL-4, in cell culture supernates indicated that the proliferating cells were TH1. Infected mature CML-DC were more effective than infected immature CML-DC, showing that T cell stimulation by mature DC and by IL-2 was additive. Discussion: CML-DC can be modified genetically and functionally by recombinant replication-defective adenoviruses, providing new possibilities for clinical trials in dendritic cell-based immunotherapy.

Original languageEnglish (US)
Pages (from-to)97-105
Number of pages9
JournalCytotherapy
Volume3
Issue number2
DOIs
StatePublished - Jan 1 2001

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ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Oncology
  • Genetics(clinical)
  • Cell Biology
  • Cancer Research
  • Transplantation

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