title: Monocytic suppressor cells derived from human peripheral blood suppress xenogenic immune reactions.
abstract: BACKGROUND
  Myeloid-derived suppressor cells (MDSC) were initially found to contribute to the immunosuppression in tumor patients and have recently been recognized as a subset of innate immune cells that are capable of regulating adaptive immunity. A variety of innate immune stimuli such as Lipopolysaccharide (LPS), which act as a double-edged sword, induce both the maturation of dendritic cells (DC) and the expansion of MDSCs.
  
  
  METHODS
  In this study, we isolated MDSCs from peripheral blood mononuclear cells and examined the suppressive effect of MDSCs against cytotoxic T lymphocyte (CTL)-mediated xenocytotoxicity.
  
  
  RESULTS
  Peripheral blood monocytes cultured in the presence of GM-CSF and IL-4 were stimulated with polyiosinic-polycytidylic acid [poly (I:C)] or LPS. Flow cytometric analyses revealed that LPS and poly I:C stimulation allows the CD33(+) CD14(+) HLA-DR(-) subset to be significantly increased. To assess the suppressive capacity of MDSCs in xenotoxicity, CTL assay was performed. Poly (I:C)-activated MDSCs dramatically suppressed the CTL xenocytotoxicity. Phagocytosis assays revealed that activated MDSCs aggressively phagocytose the xenogenic CTLs. Characterization of MDSCs by real-time PCR revealed that poly (I:C) and LPS-stimulated MDSCs expressed significant amounts of mRNA for indolamine 2,3-dioxygenase (IDO) compared to untreated MDSCs. Furthermore, when MDSCs were incubated with the IDO inhibitor, the MDSC-induced suppression of xenocytotoxicity was abolished. Taken together, the possibility that activated MDSCs could induce apoptosis in xenogenic CTLs via an IDO-dependent manner and aggressively phagocytose apoptotic CTLs cannot be excluded.
  
  
  CONCLUSIONS
  These findings indicate that MDSCs have a great deal of potential as a therapeutic strategy for dealing with xenograft rejection. Further investigations of the underlying mechanisms will facilitate the development of this therapeutic strategy.
authors.affiliation: Department of Surgery, Osaka University Graduate School of Medicine, Osaka, Japan.
authors.forename: Akira
authors.initials: A
authors.lastname: Maeda
authors.forename: Takuji
authors.initials: T
authors.lastname: Kawamura
authors.forename: Takehisa
authors.initials: T
authors.lastname: Ueno
authors.forename: Noriaki
authors.initials: N
authors.lastname: Usui
authors.forename: Shuji
authors.initials: S
authors.lastname: Miyagawa
mesh_terms: D056704:Adaptive Immunity / Q000276:immunology*; D000818:Animals; D002460:Cell Line; D003713:Dendritic Cells / Q000276:immunology; D006084:Graft Rejection / Q000517:prevention & control*; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000276:immunology*; D009000:Monocytes / Q000276:immunology*; D014183:Transplantation, Heterologous
keywords: indoleamine 2,3-dioxygenase; myeloid-derived suppressor cells; xenogenic immune reactions; xenotransplantation