title: Immature monocytes from G-CSF-mobilized peripheral blood stem cell collections carry surface-bound IL-10 and have the potential to modulate alloreactivity.
abstract: Production of the anti-inflammatory cytokine IL-10 by monocytes has been implicated as a probable negative regulator of graft-versus-host disease (GvHD) in patients undergoing allogeneic stem cell transplants (SCT). Monocytes from G-CSF-mobilized peripheral blood stem cell (gmPBSC) collections have been reported to produce more IL-10 than unmobilized monocytes in response to proinflammatory factors such as LPS. Why this should occur is unclear. In this study, monocyte phenotype and IL-10 localization and release were investigated in PB mononuclear cells (MNC) from 27 healthy donors mobilized for allogeneic SCT and from 13 patients with hematological malignancies mobilized for autologous SCT. All isolates contained elevated total percentages of monocytes in comparison with unmobilized PB, a high proportion of which displayed an immature phenotype. Stimulation of gmPB MNC with an inflammatory stimulus [fixed Staphylococcus aureus cells (SAC)] induced rapid up-regulation of CD14, indicating conversion to mature status. Localization studies indicated that IL-10 was predominantly present, bound on the surface of CD64(+)/CD14(low/neg) immature monocytes. Inflammatory stimuli (LPS, polyinosinic:polycytidylic acid, or SAC) induced release of variable quantities of IL-10 from the cell surface. MNC, separated into surface IL-10-positive or -negative fractions, differed in their ability to stimulate alloreactivity in MLR, and IL-10(+) MNC induced significantly lower levels of proliferation than IL-10(-) MNC. Thus, the subset of immature monocytes carrying surface-bound IL-10 in gmPB has the potential to modulate alloreactivity and GvHD after allogeneic SCT through cell-to-cell contact and released IL-10.
authors.affiliation: Academic Transfusion Medicine Unit, University of Glasgow, UK. af82y@clinmed.gla.ac.uk
authors.forename: A R
authors.initials: AR
authors.lastname: Fraser
authors.forename: G
authors.initials: G
authors.lastname: Cook
authors.forename: I M
authors.initials: IM
authors.lastname: Franklin
authors.forename: J G
authors.initials: JG
authors.lastname: Templeton
authors.forename: M
authors.initials: M
authors.lastname: Campbell
authors.forename: T L
authors.initials: TL
authors.lastname: Holyoake
authors.forename: J D M
authors.initials: JD
authors.lastname: Campbell
mesh_terms: D046148:Donor Selection; D006086:Graft vs Host Disease / Q000276:immunology; D016179:Granulocyte Colony-Stimulating Factor / Q000494:pharmacology*; D019650:Hematopoietic Stem Cell Mobilization / Q000379:methods*; D018380:Hematopoietic Stem Cell Transplantation; D006412:Hematopoietic Stem Cells / Q000187:drug effects / Q000276:immunology*; D006801:Humans; D016753:Interleukin-10 / Q000096:biosynthesis*; D009000:Monocytes / Q000187:drug effects / Q000276:immunology*; D010641:Phenotype; D014184:Transplantation, Homologous
chemical_list: D016753:Interleukin-10; D016179:Granulocyte Colony-Stimulating Factor