Granulocyte-colony stimulating factor drives the in vitro differentiation of human dendritic cells that induce anergy in naïve T cells.
G-CSF is a modulator of T-cell and DC functions. Previous reports show that monocytes from G-CSF-treated (post-G) healthy donors differentiate into tolerogenic DC in vitro in the presence of autologous serum, containing high levels of IL-10 and IFN-α, and in turn induce type 1 Treg (Tr1) cells. However, the direct effect of G-CSF on DC differentiation was not investigated. Here, we show that monocytes differentiated in the presence of exogenous G-CSF (G-DC) remain CD14(+) CD1a(-) , but acquire a DC-like morphology, express CD83 and CD86 and low levels of the tolerogenic markers Ig-like transcript (ILT)4 and HLA-G. G-DC spontaneously produce IL-10 and, upon stimulation, low levels of IL-12. G-DC display low stimulatory capacity and induce anergy in naïve T cells, but do not confer suppressive function. Therefore, in vitro differentiation of monocyte-derived DC in the presence of G-CSF can replicate some but not all features of post-G DC. These findings indicate that the tolerogenic properties of G-CSF do not exclusively reside in its direct effect on DC, which in turn induce T-cell anergy, but also in its ability to generate a tolerogenic milieu in vivo, which is necessary for Tr1 cell induction and cannot be replicated in vitro.
San Raffaele Telethon Institute for Gene Therapy, Department of Regenerative Medicine, Stem Cells and Gene Therapy, San Raffaele Scientific Institute, Milan, Italy.
Maura
M
Rossetti
Silvia
S
Gregori
Maria Grazia
MG
Roncarolo
D015703:Antigens, CD / Q000276:immunology; D002454:Cell Differentiation / Q000187:drug effects / Q000276:immunology*; D017635:Clonal Anergy / Q000187:drug effects / Q000276:immunology*; D003713:Dendritic Cells / Q000166:cytology / Q000276:immunology*; D005786:Gene Expression Regulation / Q000187:drug effects / Q000276:immunology; D016179:Granulocyte Colony-Stimulating Factor / Q000276:immunology* / Q000494:pharmacology; D006680:HLA Antigens / Q000276:immunology; D059951:HLA-G Antigens; D015395:Histocompatibility Antigens Class I / Q000276:immunology; D006801:Humans; D007136:Immunoglobulins / Q000276:immunology; D016898:Interferon-alpha / Q000276:immunology; D016753:Interleukin-10 / Q000276:immunology; D018664:Interleukin-12 / Q000276:immunology; D008562:Membrane Glycoproteins / Q000276:immunology; D009000:Monocytes / Q000166:cytology / Q000276:immunology*; D011971:Receptors, Immunologic / Q000276:immunology; D050378:T-Lymphocytes, Regulatory / Q000166:cytology / Q000276:immunology*; D000097802:CD83 Antigen
D015703:Antigens, CD; D016179:Granulocyte Colony-Stimulating Factor; D006680:HLA Antigens; D059951:HLA-G Antigens; D015395:Histocompatibility Antigens Class I; D007136:Immunoglobulins; D016898:Interferon-alpha; D016753:Interleukin-10; D018664:Interleukin-12; D008562:Membrane Glycoproteins; D011971:Receptors, Immunologic; D000097802:CD83 Antigen; C508609:IL10 protein, human; C491341:LILRB2 protein, human