Induction of dendritic cells with IFN-alpha and GM-CSF from bone marrow mononuclear cells from patients with chronic myeloid leukemia / 中国病理生理杂志

ABSTRACT

AIM: To investigate the effects of interferon-alpha (IFN-?) on the development of dendritic cells (DCs) derived from bone marrow mononuclear cells in patients with chronic myeloid leukemia (CML). METHODS: Bone marrow mononuclear cells from 12 CML patients were cultured initially using cytokines as follows recombined human granulocyte-macrophage colony stimulating factor (rhGM-CSF) plus IFN-? (IFN-?-DCs); rhGM-CSF plus recombined human interleukin-4 (rhIL-4) (IL-4-DCs); IFN-? alone; rhGM-CSF alone in 10% FBS RPMI-1640 medium for 7 days and then recombined human tumor necrosis factor-? (rhTNF-?) was added for another 3 days. The morphologic features were observed by Wright's staining under inverted microscope. CD_ 80,CD_ 86,CD_ 83,CD_ 1a and HLA-DR expression were assayed by flow cytometry. Cytogenetic analysis was performed for one CML patient by fluorescence in-situ hybridization (FISH), and the functions of antigen presenting were tested by mixed lymphocyte reaction (MLR). RESULTS: IFN-?-DCs displayed features in morphology that was similar to those of IL-4-DCs with delicate membrane projections. IFN-?-DCs showed an increase in expression of CD80, CD86, CD83, HLA-DR and more intense abilities of allogeneic antigen presentation with and without rhTNF-? stimulation, compared with the control groups of IL-4-DCs. FISH confirmed the DCs of both groups were leukemic origin. CONCLUSIONS: (1) IFN-? promoted the differentiation/activation of bone marrow mononuclear cells from patients with CML into activated dendritic cells. (2) The phenomenon of generation of activated DCs in vitro might contribute to therapeutic effect of IFN-? in CML. (3) IFN-? may be valuable for the generation of active bone marrow mononuclear cells-derived DCs to be as vaccination strategies of CML patients.