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Granulocyte–macrophage colony‐stimulating factor drives monocytes to CD14 low CD83 + DCSIGN – interleukin‐10‐producing myeloid cells with differential effects on T‐cell subsets
Author(s) -
Ganguly Dipyaman,
Paul Kausik,
Bagchi Jayashree,
Rakshit Srabanti,
Mandal Labanya,
Bandyopadhyay Gautam,
Bandyopadhyay Santu
Publication year - 2007
Publication title -
immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.297
H-Index - 133
eISSN - 1365-2567
pISSN - 0019-2805
DOI - 10.1111/j.1365-2567.2007.02596.x
Subject(s) - granulocyte macrophage colony stimulating factor , cd14 , cd40 , haematopoiesis , interleukin 3 , monocyte , t cell , biology , cytokine , microbiology and biotechnology , myeloid , immunology , chemistry , cytotoxic t cell , antigen presenting cell , immune system , stem cell , in vitro , biochemistry
Summary 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‐α, interferon‐γ 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.