title: Transgenic interleukin 2 secreted by CML dendritic cells stimulates autologous T(H)1 T cells.
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 eta, but not of IL-4, in cell culture supernates indicated that the proliferating cells were T(H)1. 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.
  
  
  CONCLUSIONS
  CML-DC can be modified genetically and functionally by recombinant replication-defective adenoviruses, providing new possibilities for clinical trials in dendritic cell-based immunotherapy.
authors.affiliation: Stem Cell Laboratory, Mayo Clinic Cancer Center, Rochester, MN 55905, USA.
authors.forename: A B
authors.initials: AB
authors.lastname: Dietz
authors.forename: M R
authors.initials: MR
authors.lastname: Litzow
authors.forename: P A
authors.initials: PA
authors.lastname: Bulur
authors.forename: S
authors.initials: S
authors.lastname: Vuk-Pavlović
mesh_terms: D000256:Adenoviridae; D017951:Antigen Presentation; D003713:Dendritic Cells / Q000276:immunology* / Q000378:metabolism; D018014:Gene Transfer Techniques; D005822:Genetic Vectors; D007167:Immunotherapy / Q000379:methods*; D007371:Interferon-gamma / Q000378:metabolism; D007376:Interleukin-2 / Q000235:genetics / Q000378:metabolism*; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000276:immunology / Q000378:metabolism / Q000628:therapy*; D011995:Recombination, Genetic; D018417:Th1 Cells / Q000276:immunology* / Q000378:metabolism; D014407:Tumor Cells, Cultured
chemical_list: D007376:Interleukin-2; D007371:Interferon-gamma