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.

journal_name

Immunology

journal_title

Immunology

authors

Rasaiyaah J,Noursadeghi M,Kellam P,Chain B

doi

10.1111/j.1365-2567.2008.03018.x

subject

Has Abstract

pub_date

2009-07-01 00:00:00

pages

429-41

issue

3

eissn

0019-2805

issn

1365-2567

pii

IMM3018

journal_volume

127

pub_type

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