title: Phenotypic and functional deficiencies of leukaemic dendritic cells from patients with chronic myeloid leukaemia.
abstract: 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.
authors.affiliation: Laboratory for Tumour and Immunobiology, Division of Haematology and Oncology, Innsbruck University Hospital, Innsbruck, Austria. klaus.eisendle@uibk.ac.at
authors.forename: Klaus
authors.initials: K
authors.lastname: Eisendle
authors.forename: Alois
authors.initials: A
authors.lastname: Lang
authors.forename: Brigitte
authors.initials: B
authors.lastname: Eibl
authors.forename: David
authors.initials: D
authors.lastname: Nachbaur
authors.forename: Herta
authors.initials: H
authors.lastname: Glassl
authors.forename: Michael
authors.initials: M
authors.lastname: Fiegl
authors.forename: Joseph
authors.initials: J
authors.lastname: Thaler
authors.forename: Guenther
authors.initials: G
authors.lastname: Gastl
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D016022:Case-Control Studies; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000276:immunology*; D004705:Endocytosis; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D016130:Immunophenotyping; D007376:Interleukin-2 / Q000378:metabolism; D015847:Interleukin-4 / Q000378:metabolism; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000276:immunology*; D007958:Leukocyte Count; D008070:Lipopolysaccharides / Q000494:pharmacology; D007959:Lymphocyte Culture Test, Mixed; D008297:Male; D008875:Middle Aged; D018709:Statistics, Nonparametric; D013601:T-Lymphocytes / Q000276:immunology; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D007376:Interleukin-2; D008070:Lipopolysaccharides; D014409:Tumor Necrosis Factor-alpha; D015847:Interleukin-4