Transcriptional and functional defects of dendritic cells derived from the MUTZ-3 leukaemia line

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-tra...

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Bibliographic Details
Published in:	Immunology 2009-07, Vol.127 (3), p.429-441
Main Authors:	Rasaiyaah, Jane, Noursadeghi, Mahdad, Kellam, Paul, Chain, Benjamin
Format:	Article
Language:	eng
Subjects:	acute myeloid leukaemia antigen presentation Antigen Presentation - immunology Cell Differentiation - immunology Cell Proliferation dendritic cells Dendritic Cells - immunology Down-Regulation - immunology Gene Expression - immunology Humans Immunophenotyping Leukemia, Myeloid, Acute - genetics Leukemia, Myeloid, Acute - immunology Lipopolysaccharide Receptors - analysis Multigene Family - immunology Original Reverse Transcriptase Polymerase Chain Reaction - methods Transcription, Genetic - immunology Tumor Cells, Cultured tumour immunity
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Summary:	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.
ISSN:	0019-2805 1365-2567