Transgenic interleukin 2 secreted by CML dendritic cells stimulates autologous T(H)1 T cells

Background We investigated if dendritic cells (DC), derived from patients suffering fr om chronic myeloid leukemia (CML) could be modified by recombinant replicat ion-defective adenoviruses to express functional interleukin 2 (IL-2). Such modification might confer onto antigen-presenting cells the ability to sti mulate expansion of effector cells. Methods To quantify the infection efficiency of CML dendritic cells (CML-DC) by rec ombinant adenovirus, we measured the expression of green fluorescent protei n (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 st imulate proliferation of autologous T cells. Results Uninfected CML-DC and normal DC secreted similar amounts of IL-12 and stimu lated similarly efficient autologous mixed leukocyte reaction. Immature CML -DC infected by an adenovirus containing the gene for IL-2 secreted large a mounts of IL-2 and stimulated proliferation of autologous T cells more effi ciently than the corresponding CML-DC alone. High levels of interferon eta, but not of IL-4, in cell culture supernates indicated that the proliferati ng cells were T(H)1. Infected mature CML-DC were more effective than infect ed 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 replicat ion-defective adenoviruses, providing new possibilities for clinical trials in dendritic cell-based immunotherapy.