title: Transcriptional and functional defects of dendritic cells derived from the MUTZ-3 leukaemia line.
abstract: Dendritic cells (DC) generated from MUTZ-3, an immortalized acute myeloid leukaemia-derived cell line, have potential application as a model for the study of human DC, and as a tool with which to stimulate immunotherapeutic responses to cancer. However, the relationship of MUTZ-3 DC to their non-transformed counterparts remains incompletely understood. Immunoselected CD14+ MUTZ-3 cells were used to generate a homogeneous population of DC (M3DC). These cells had a cell surface phentoype and morphology characteristic of conventional monocyte-derived DC (MDDC). Whole genome transcriptome comparison of M3DC and MDDC however, revealed extensive differences between these two cell types. Functional ontology-based data analysis revealed three enriched clusters of genes downregulated in M3DC, with functions in pathogen recognition, DC maturation and cytokine/chemokine signalling. Downregulation of protein expression was confirmed for several of these genes. The molecular differences were accompanied by a profoundly impaired phenotypic and functional response of M3DC to microbial stimulation. The immortalized phenotype of MUTZ-3 therefore reflects not only deregulated proliferative capacity, but substantial perturbation of normal antigen-presenting cell function. These results have important implications for studies using MUTZ-3 as a model of MDDC or for cancer immunotherapy.
authors.affiliation: Division of Infection and Immunity, University College London, London, UK.
authors.forename: Jane
authors.initials: J
authors.lastname: Rasaiyaah
authors.forename: Mahdad
authors.initials: M
authors.lastname: Noursadeghi
authors.forename: Paul
authors.initials: P
authors.lastname: Kellam
authors.forename: Benjamin
authors.initials: B
authors.lastname: Chain
mesh_terms: D017951:Antigen Presentation / Q000276:immunology; D002454:Cell Differentiation / Q000276:immunology; D049109:Cell Proliferation; D003713:Dendritic Cells / Q000276:immunology*; D015536:Down-Regulation / Q000276:immunology; D015870:Gene Expression / Q000276:immunology; D006801:Humans; D016130:Immunophenotyping; D015470:Leukemia, Myeloid, Acute / Q000235:genetics / Q000276:immunology*; D018950:Lipopolysaccharide Receptors / Q000032:analysis; D005810:Multigene Family / Q000276:immunology; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D014158:Transcription, Genetic / Q000276:immunology; D014407:Tumor Cells, Cultured
chemical_list: D018950:Lipopolysaccharide Receptors