Granulocyte–macrophage colony‐stimulating factor drives monocytes to CD14low CD83+ DCSIGN– interleukin‐10‐producing myeloid cells with differential effects on T‐cell subsets

Abstract

Granulocyte-macrophage colony-stimulating factor (GM-CSF) has long been found to have growth-promoting effects on multipotent haematopoietic lineages, specifically granulocytes and macrophages. GM-CSF combined with interleukin-4 (IL-4) drives monocytes to become myeloid dendritic cells (mDCs) in vitro. We report that culturing human monocytes with GM-CSF alone generates myeloid cells (GM-Mono) that have lower expression of CD14 than monocytes and that fail to express DC-SIGN. GM-Monos, however, express CD83 and the transcription factor PU.1, although at a lower level than the conventional mDCs generated in the presence of GM-CSF and IL-4. On stimulation with tumour necrosis factor-alpha, interferon-gamma and anti-CD40 monoclonal antibody, the GM-Monos predominantly produced IL-10 but were less efficient in IL-12 production. In a primary allogeneic mixed lymphocyte reaction, GM-Monos induced hyporesponsiveness and IL-10-biased cytokine production in CD4(+) T cells. In fresh mixed lymphocyte reaction, GM-Monos inhibited conventional mDC-induced allogeneic CD4(+) T-cell proliferation. GM-Mono-induced inhibition of allogeneic CD4(+) T-cell proliferation was partially attributed to IL-10. Interestingly, GM-Monos neither induced hyporesponsiveness in allogeneic CD8(+) T cells nor inhibited conventional mDC-induced allogeneic CD8(+) T-cell proliferation. Taken together, we characterize monocyte-derived CD14(low) CD83(+) cells generated by GM-CSF that can induce tolerance or stimulation of T cells depending on T-cell subsets.