| Phenotypic and functional deficiencies of leukaemic dendritic cells from patients with chronic myeloid leukaemia. | |
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MedLine Citation:
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PMID: 12492578 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Chronic myeloid leukaemia (CML) dendritic cells (DC) are possible candidates for inducing antileukaemic immunity. This study aimed to investigate the frequency, phenotype and function of blood-derived leukaemic DC in comparison with DC from healthy donors using flow cytometric assays and mixed leucocyte reaction (MLR). Immature leukaemic DC displayed a reduced endocytotic capacity as compared with healthy controls. Moreover, in vitro maturation of leukaemic DC was found to be deficient. Expression of CD80, CD83, CD86, and major histocompatibility complex class I and class II antigens were reduced on lipopolysaccharide (LPS)-matured leukaemic DC but were enhanced by a mixture of interleukin 1beta (IL-1beta), IL-6, tumour necrosis factor-alpha (TNF-alpha) and prostaglandin E2 (PGE2). Upon stimulation with bacterial LPS, intracellular TNF-alpha and IL-8 production was diminished in maturing DC from CML patients. This distinct cytokine deficiency was overcome when leukaemic DC were stimulated with cytokines/PGE2. MLR showed fully functional leukaemic DC after TNF-alpha-induced maturation, but a reduced proliferative alloresponse of leukaemic peripheral blood mononuclear cells. Further, intracellular production of cytokines in CML-derived T cells was markedly reduced. These data indicated that, in CML, the maturation response of leukaemic monocyte-derived DC to a natural stimulus like LPS is abnormal and may be caused by an aberrant TNF-alpha response in these cells. Thus, TNF-alpha alone or in combination with pro-inflammatory and T-cell stimulatory cytokines should be considered as an adjuvant for DC-based immunotherapy in CML. |
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Authors:
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Klaus Eisendle; Alois Lang; Brigitte Eibl; David Nachbaur; Herta Glassl; Michael Fiegl; Joseph Thaler; Guenther Gastl |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't |
Journal Detail:
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Title: British journal of haematology Volume: 120 ISSN: 0007-1048 ISO Abbreviation: Br. J. Haematol. Publication Date: 2003 Jan |
Date Detail:
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Created Date: 2002-12-20 Completed Date: 2003-02-05 Revised Date: 2007-11-15 |
Medline Journal Info:
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Nlm Unique ID: 0372544 Medline TA: Br J Haematol Country: England |
Other Details:
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Languages: eng Pagination: 63-73 Citation Subset: IM |
Affiliation:
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Laboratory for Tumour and Immunobiology, Division of Haematology and Oncology, Innsbruck University Hospital, Innsbruck, Austria. klaus.eisendle@uibk.ac.at |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Adolescent Adult Aged Aged, 80 and over Case-Control Studies Cells, Cultured Dendritic Cells / immunology* Endocytosis Female Flow Cytometry Humans Immunophenotyping Interleukin-2 / metabolism Interleukin-4 / metabolism Leukemia, Myelogenous, Chronic, BCR-ABL Positive / immunology* Leukocyte Count Lipopolysaccharides / pharmacology Lymphocyte Culture Test, Mixed Male Middle Aged Statistics, Nonparametric T-Lymphocytes / immunology Tumor Necrosis Factor-alpha / metabolism |
| Chemical | |
Reg. No./Substance:
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0/Interleukin-2; 0/Lipopolysaccharides; 0/Tumor Necrosis Factor-alpha; 207137-56-2/Interleukin-4 |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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