LAG-3 (CD223) reduces macrophage and dendritic cell differentiation from monocyte precursors.
Major histocompatibility complex (MHC) class II molecules expressed on monocytes may play a role in the control of differentiation of antigen-presenting cells. A soluble LAG-3 (CD223) molecule (sLAG-3) is a natural, high-affinity ligand for MHC class II. It is known to induce maturation of monocyte-derived dendritic cells in vitro and is used as a vaccine adjuvant to induce CD4 T helper type 1 responses and CD8 T-cell responses in vivo. Here, we demonstrate that sLAG-3 (but not an MHC class II-specific monoclonal antibody) reduces the differentiation of monocytes into macrophages in the presence of granulocyte-macrophage colony-stimulating factor (GM-CSF) as well as their differentiation into dendritic cells in the presence of GM-CSF and interleukin-4, as shown by a decrease in CD14 and CD1a expression, respectively. Dendritic cells derived from monocytes in the presence of sLAG-3 showed impaired antigen-presentation function, as assessed by the reduced capability to induce proliferation of T cells. Our results suggest that activated LAG-3(+) lymphocytes present at sites of inflammation may reduce the differentiation of monocytes into macrophages or fully competent antigen-presenting dendritic cells, thus limiting the magnitude of the ongoing T-cell immune responses.
Buisson
Sandrine
S
Faculté de Pharmacie, Université Paris-Sud, Châtenay-Malabry, France.
Triebel
Frédéric
F
D017951:Antigen Presentation / Q000276:immunology; D000938:Antigen-Presenting Cells / Q000166:cytology / Q000276:immunology*; D015703:Antigens, CD / Q000276:immunology*; D018949:Antigens, CD1 / Q000097:blood; D002454:Cell Differentiation / Q000276:immunology; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000166:cytology / Q000276:immunology; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000276:immunology; D000949:Histocompatibility Antigens Class II / Q000097:blood; D006801:Humans; D015847:Interleukin-4 / Q000276:immunology; D008024:Ligands; D018950:Lipopolysaccharide Receptors / Q000097:blood; D008213:Lymphocyte Activation / Q000276:immunology; D008264:Macrophages / Q000166:cytology / Q000276:immunology; D009000:Monocytes / Q000166:cytology / Q000276:immunology*; D011994:Recombinant Proteins / Q000276:immunology; D000093322:Lymphocyte Activation Gene 3 Protein
D015703:Antigens, CD; D018949:Antigens, CD1; C419393:CD1a antigen; D000949:Histocompatibility Antigens Class II; D008024:Ligands; D018950:Lipopolysaccharide Receptors; D011994:Recombinant Proteins; D015847:Interleukin-4; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D000093322:Lymphocyte Activation Gene 3 Protein; C000720326:Lag3 protein, human; C000720328:soluble LAG-3 protein, human
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