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Open Access Green as soon as Postprint is submitted to ZB.
Differential effects of ifosfamide on dendritic cell-mediated stimulation of T cell interleukin-2 production, natural killer cell cytotoxicity and interferon-gamma production.
Clin. Exp. Immunol. 153, 429-438 (2008)
Ifosfamide is a DNA-alkylating agent used frequently in chemotherapy of human malignancies. Ifosfamide and its major decomposition products deplete intracellular glutathione (GSH). Glutathione is the major intracellular thiol reductant that protects cells against oxidative injury. Ifosfamide depletion of intracellular GSH in human dendritic cells (DC), T cells and natural killer (NK) cells impairs their functional activity which can be restored by reconstituting GSH. Here we assessed the effect of ifosfamide on DC-mediated stimulation of NK cell proliferation via T cells and on direct DC stimulation of NK cell cytotoxicity and interferon (IFN)-gamma production. Indirect DC stimulation of NK cell proliferation via T cells and T cell-derived interleukin (IL)-2 were reduced by ifosfamide treatment of DC and reconstitution of GSH in DC restored both responses. When DC and NK cells were treated with ifosfamide, DC could overcome the negative effect of ifosfamide on NK cytotoxic function whereas NK cell IFN-gamma production was less efficiently restored. The ability of IL-2 activated NK cells to kill autologous immature DC or to induce DC maturation was reduced moderately by treatment of both cell types with ifosfamide. Overall, our results suggest that DC may stimulate anti-tumour effector cells in patients even if they had received treatment with chemotherapeutic agents such as ifosfamide.
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0.970
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7
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Publication type
Article: Journal article
Document type
Scientific Article
Keywords
Cytotoxicity ; Dendritic Cells ; Ifosfamide ; Nk Cells ; Proliferation
Language
Publication Year
2008
HGF-reported in Year
2008
ISSN (print) / ISBN
0009-9104
e-ISSN
1365-2249
Quellenangaben
Volume: 153,
Issue: 3,
Pages: 429-438
Publisher
Wiley
Reviewing status
Peer reviewed
Institute(s)
Institute of Molecular Immunology (IMI)
POF-Topic(s)
30504 - Mechanisms of Genetic and Environmental Influences on Health and Disease
Research field(s)
Immune Response and Infection
PSP Element(s)
G-501700-006
Scopus ID
49649106033
Erfassungsdatum
2008-08-20