title: Immunosuppressive properties of mitomycin C-incubated human myeloid blood cells (MIC) in vitro.
abstract: 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.
authors.affiliation: Department of Transplantation Immunology, Institute for Immunology, University of Heidelberg, Im Neuenheimer Feld 305, 69120 Heidelberg, Germany. Electronic address: lauradittmar@gmx.de.
authors.forename: Laura
authors.initials: L
authors.lastname: Dittmar
authors.affiliation: Department of Transplantation Immunology, Institute for Immunology, University of Heidelberg, Im Neuenheimer Feld 305, 69120 Heidelberg, Germany. Electronic address: em_mohr@t-online.de.
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Mohr
authors.affiliation: Department of Transplantation Immunology, Institute for Immunology, University of Heidelberg, Im Neuenheimer Feld 305, 69120 Heidelberg, Germany. Electronic address: christian.kleist@med.uni-heidelberg.de.
authors.forename: Christian
authors.initials: C
authors.lastname: Kleist
authors.affiliation: Department of Transplantation Immunology, Institute for Immunology, University of Heidelberg, Im Neuenheimer Feld 305, 69120 Heidelberg, Germany. Electronic address: ehser@42ls.com.
authors.forename: Sandra
authors.initials: S
authors.lastname: Ehser
authors.affiliation: Department of Transplantation Immunology, Institute for Immunology, University of Heidelberg, Im Neuenheimer Feld 305, 69120 Heidelberg, Germany. Electronic address: haydarutku@yahoo.com.
authors.forename: Haydar
authors.initials: H
authors.lastname: Demirdizen
authors.affiliation: Department of Transplantation Immunology, Institute for Immunology, University of Heidelberg, Im Neuenheimer Feld 305, 69120 Heidelberg, Germany. Electronic address: Flavius.Sandra-Petrescu@umm.de.
authors.forename: Flavius
authors.initials: F
authors.lastname: Sandra-Petrescu
authors.affiliation: Department of Internal Medicine V, University of Heidelberg, Im Neuenheimer Feld 410, 69120 Heidelberg, Germany. Electronic address: michael.hundemer@med.uni-heidelberg.de.
authors.forename: Michael
authors.initials: M
authors.lastname: Hundemer
authors.affiliation: Department of Transplantation Immunology, Institute for Immunology, University of Heidelberg, Im Neuenheimer Feld 305, 69120 Heidelberg, Germany. Electronic address: gerhard.opelz@med.uni-heidelberg.de.
authors.forename: Gerhard
authors.initials: G
authors.lastname: Opelz
authors.affiliation: Department of Transplantation Immunology, Institute for Immunology, University of Heidelberg, Im Neuenheimer Feld 305, 69120 Heidelberg, Germany. Electronic address: esa.germany@gmx.org.
authors.forename: Peter
authors.initials: P
authors.lastname: Terness
mesh_terms: D017209:Apoptosis / Q000187:drug effects; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000187:drug effects; D006801:Humans; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D016685:Mitomycin / Q000494:pharmacology*; D009000:Monocytes / Q000166:cytology / Q000187:drug effects / Q000528:radiation effects; D022423:Myeloid Cells / Q000187:drug effects*; D013601:T-Lymphocytes / Q000276:immunology
chemical_list: D007166:Immunosuppressive Agents; D016685:Mitomycin
keywords: Cell therapy; Organ transplantation; Specific immunosuppression; Suppressive cells; Tolerance induction