Objective. The incidence and severity of acute graft-vs-host disease after allogeneic transplantation of granulocyte colony-stimulating factor (G-CSF)-mobilized peripheral blood stem cells (PBSC) are not greater than those after conventional bone marrow transplantation despite infusion of more than one log greater number of donor T cells in PBSC. It has been postulated that monocytes from G-CSF-mobilized donors suppress alloreactivity of donor T cells. Materials and Methods. We investigated the phenotype and function of monocytes in normal individuals receiving 10 μg/kg of G-CSF for 4 days. Results. Monocytes were phenotypically and functionally different after G-CSF administration from steady-state monocytes. They were characterized by an increased CD14+CD16+ subpopulation, reduced expression of HLA-DR, and diminished ability to produce tumor necrosis factor-α and interleukin-10 to lipopolysaccharide, compared with steady-state monocytes. These alterations were not replicated by culturing monocytes with G-CSF in vitro, suggesting an indirect effect of G-CSF. In addition, the antigen-presenting function of G-CSF-mobilized monocytes was impaired. Conclusion. Hyporesponsiveness of G-CSF-treated monocytes to lipopolysaccharide with regard to tumor necrosis factor-α production, together with impaired antigen-presenting function, may be responsible for the unexpectedly low incidence of graft-vs-host disease after G-CSF-mobilized PBSC transplantation.
All Science Journal Classification (ASJC) codes
- Molecular Biology
- Cell Biology
- Cancer Research