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.
Rossetti
Maura
M
San Raffaele Telethon Institute for Gene Therapy, Department of Regenerative Medicine, Stem Cells and Gene Therapy, San Raffaele Scientific Institute, Milan, Italy.
Gregori
Silvia
S
Roncarolo
Maria Grazia
MG
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