Immunosuppressive properties of mitomycin C-incubated human myeloid blood cells (MIC) in vitro

Previous animal studies showed that donor-derived blood cells treated with mitomycin C (MMC) prolong allograft survival when injected into recipients. This model was effective with whole blood, peripheral blood mononuclear cells (PBMC) (monocytes being the active cell subpopulation) or dendritic cel...

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Main Authors: Dittmar, Laura (Author) , Mohr, Elisabeth (Author) , Kleist, Christian (Author) , Ehser, Sandra (Author) , Demirdizen, Haydar (Author) , Şandra-Petrescu, Flavius Ionuţ (Author) , Hundemer, Michael (Author) , Opelz, Gerhard (Author) , Terness, Peter (Author)
Format: Article (Journal)
Language:English
Published: 11 June 2015
In: Human immunology
Year: 2015, Volume: 76, Issue: 7, Pages: 480-487
ISSN:1879-1166
DOI:10.1016/j.humimm.2015.06.008
Online Access:Verlag, lizenzpflichtig, Volltext: https://doi.org/10.1016/j.humimm.2015.06.008
Verlag, lizenzpflichtig, Volltext: http://www.sciencedirect.com/science/article/pii/S0198885915001743
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Author Notes:Laura Dittmar, Elisabeth Mohr, Christian Kleist, Sandra Ehser, Haydar Demirdizen, Flavius Sandra-Petrescu, Michael Hundemer, Gerhard Opelz, Peter Terness
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Summary:Previous animal studies showed that donor-derived blood cells treated with mitomycin C (MMC) prolong allograft survival when injected into recipients. This model was effective with whole blood, peripheral blood mononuclear cells (PBMC) (monocytes being the active cell subpopulation) or dendritic cells. In view of a potential clinical application, we study now the immunosuppressive properties of human myeloid cells in vitro. Mature dendritic cells (generated from naïve monocytes) or monocytes treated with mitomycin C do not or only weakly inhibit allogeneic T cells in vitro, whereas cells in an early differentiation state between monocytes and DC exert suppressive activity when treated with MMC. In contrast, DC generated from MMC-treated monocytes show the morphology and phenotype of early immature DC (iDC) and suppress T-cell responses. It is known that untreated monocytes injected into a recipient encounter a cytokine milieu which differentiates them to stimulatory DC. In our in vitro experiment MMC-treated monocytes cultured in a DC-maturing milieu transform themselves into suppressive early iDC. This reproduces a process which takes place when administering MMC-monocytes to a recipient. In conclusion, human MMC-DC or MMC-monocytes are not or only weakly suppressive in vitro. When MMC-monocytes are differentiated to DC the resulting cells become suppressive.
Item Description:Gesehen am 02.06.2020
Physical Description:Online Resource
ISSN:1879-1166
DOI:10.1016/j.humimm.2015.06.008