Granulocyte-macrophage colony-stimulating factor drives monocytes to CD14low CD83+ DCSIGN- interleukin-10-producing myeloid cells with differential effects on T-cell subsets.
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.
Ganguly
Dipyaman
D
The Infectious Diseases and Immunology Division, Indian Institute of Chemical Biology, Kolkata, India.
Paul
Kausik
K
Bagchi
Jayashree
J
Rakshit
Srabanti
S
Mandal
Labanya
L
Bandyopadhyay
Gautam
G
Bandyopadhyay
Santu
S
D015703:Antigens, CD / Q000032:analysis; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D015815:Cell Adhesion Molecules / Q000032:analysis; D002454:Cell Differentiation / Q000276:immunology; D049109:Cell Proliferation; D002478:Cells, Cultured; D005434:Flow Cytometry; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000276:immunology*; D006801:Humans; D007108:Immune Tolerance / Q000276:immunology; D007136:Immunoglobulins / Q000032:analysis; D016753:Interleukin-10 / Q000096:biosynthesis; D037181:Lectins, C-Type / Q000032:analysis; D018950:Lipopolysaccharide Receptors / Q000032:analysis; D007959:Lymphocyte Culture Test, Mixed; D008562:Membrane Glycoproteins / Q000032:analysis; D009000:Monocytes / Q000276:immunology*; D010587:Phagocytosis / Q000276:immunology; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D011956:Receptors, Cell Surface / Q000032:analysis; D016176:T-Lymphocyte Subsets / Q000276:immunology*; D051195:Toll-Like Receptor 2 / Q000378:metabolism; D051197:Toll-Like Receptor 4 / Q000378:metabolism; D015534:Trans-Activators / Q000378:metabolism; D000097802:CD83 Antigen; D000099232:Proto-Oncogene Protein Spi-1; D000099215:DC-Specific ICAM-3 Grabbing Nonintegrin
D015703:Antigens, CD; D015815:Cell Adhesion Molecules; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D007136:Immunoglobulins; D016753:Interleukin-10; D037181:Lectins, C-Type; D018950:Lipopolysaccharide Receptors; D008562:Membrane Glycoproteins; D011518:Proto-Oncogene Proteins; D011956:Receptors, Cell Surface; D051195:Toll-Like Receptor 2; D051197:Toll-Like Receptor 4; D015534:Trans-Activators; D000097802:CD83 Antigen; D000099232:Proto-Oncogene Protein Spi-1; D000099215:DC-Specific ICAM-3 Grabbing Nonintegrin; C495345:TLR4 protein, human