GMCSF in the absence of other cytokines sustains human dendritic cell precursors with T cell regulatory activity and capacity to differentiate into functional dendritic cells.
Dendritic cell precursors, from human peripheral blood, express epitopes reactive with monoclonal antibodies specific for the empty conformation of HLA-DR1. Expression is substantially up-regulated during GMCSF-induced differentiation to immature dendritic cells, but is strongly down-regulated by IL-4. In the conventional protocol for in vitro generation of human dendritic cells from monocyte precursors, both GMCSF and IL-4 are used together, with IL-4 thought to have an effect on preventing macrophage outgrowth but not substantially altering the dendritic cell maturation pathway, whereas conventional protocols for generation of murine dendritic cells use GMCSF alone. We characterized human monocytes cultured in the presence of GMCSF and in the absence of IL-4, and found that the resultant cultures are stable for long periods in vitro, and have T cell stimulatory and immunodulatory activity characteristic of immature dendritic cells. Their response to maturation stimuli is weak in the absence of IL-4 but these cells retain the ability to differentiate into fully functional mature dendritic cells upon IL-4 treatment. We suggest that these cells may provide a useful model to investigate tolerogenic function as a developmental feature of DC and to understand molecular events involved in IL-4 priming for maturation.
Chitta
Sriram
S
University of Massachusetts Medical School, Department of Pathology, Worcester, MA 10655, United States.
Santambrogio
Laura
L
Stern
Lawrence J
LJ
D017951:Antigen Presentation / Q000276:immunology; D015703:Antigens, CD; D000943:Antigens, Differentiation; D000956:Antigens, Viral / Q000276:immunology / Q000378:metabolism; D002454:Cell Differentiation / Q000276:immunology; D019070:Cell Lineage; D003713:Dendritic Cells / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D004306:Dose-Response Relationship, Immunologic; D000939:Epitopes; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000276:immunology / Q000378:metabolism; D015798:HLA-DR1 Antigen / Q000235:genetics / Q000276:immunology; D006801:Humans; D007155:Immunologic Factors / Q000276:immunology; D016130:Immunophenotyping; D015847:Interleukin-4 / Q000276:immunology / Q000378:metabolism; D011994:Recombinant Proteins / Q000276:immunology / Q000378:metabolism; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology / Q000378:metabolism
D015703:Antigens, CD; D000943:Antigens, Differentiation; D000956:Antigens, Viral; D000939:Epitopes; D015798:HLA-DR1 Antigen; D007155:Immunologic Factors; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha; D015847:Interleukin-4; D016178:Granulocyte-Macrophage Colony-Stimulating Factor