Culture of bone marrow cells in GM-CSF plus high doses of lipopolysaccharide generates exclusively immature dendritic cells which induce alloantigen-specific CD4 T cell anergy in vitro.
Dendritic cells (DC) can be generated from mouse bone marrow (BM) in the presence of granulocyte-macrophage colony-stimulating factor (GM-CSF). Bacterial stimuli such as endotoxin / lipopolysaccharide (LPS) can induce their final maturation. When BM-DC cultures were treated at day 6 or later with LPS, this final maturation was induced in vitro within 24 h. Such mature DC exhibited high levels of surface MHC II molecules and potent T cell sensitizing, but reduced endocytosis capacity. In contrast, immature DC express only few MHC II molecules and are weak T cell stimulators but highly endocytic. When BM-DC cultures in GM-CSF were treated with 1 microg / ml LPS at day 0 of the culture or throughout the culture, only immature DC developed as defined by phenotype (MHC II low) and function (high endocytosis, weak primary mixed lymphocyte reaction). Those early LPS-treated immature DC induced alloantigen-specific anergy of CD4(+) T cells in vitro. These findings might contribute to the understanding of reduced T cell immunity in the course of septic shock and find application in DC-mediated tolerogenic immunotherapy strategies.
Lutz
M B
MB
Department of Dermatology, University of Erlangen-Nuremberg, Erlangen, Germany. lutz@derma.med.uni-erlangen.de
Kukutsch
N A
NA
Menges
M
M
Rössner
S
S
Schuler
G
G
D000818:Animals; D001854:Bone Marrow Cells / Q000166:cytology / Q000187:drug effects*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D002454:Cell Differentiation / Q000187:drug effects; D002478:Cells, Cultured; D017635:Clonal Anergy / Q000276:immunology*; D003713:Dendritic Cells / Q000166:cytology / Q000187:drug effects / Q000276:immunology*; D004306:Dose-Response Relationship, Immunologic; D004705:Endocytosis / Q000187:drug effects / Q000276:immunology; D005434:Flow Cytometry; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000494:pharmacology*; D000949:Histocompatibility Antigens Class II / Q000032:analysis; D007519:Isoantigens / Q000276:immunology*; D008070:Lipopolysaccharides / Q000276:immunology*; D051379:Mice; D008815:Mice, Inbred Strains; D010641:Phenotype; D013997:Time Factors
D000949:Histocompatibility Antigens Class II; D007519:Isoantigens; D008070:Lipopolysaccharides; D016178:Granulocyte-Macrophage Colony-Stimulating Factor