Abstract
The influence of GM+IL-4 and Flt3 ligand (FL) on phenotype and function of BM-derived DC from Lewis rats was investigated. GM+IL-4-induced DC, despite expression of CD80/CD86, were less stimulatory than FL-induced DC that expressed low CD80/CD86 and were efficient stimulators of allogeneic T cells. GM+IL-4 DC were CD11b+ OX62lo, whereas FL DC were CD11blo OX62+. Following activation, GM+IL-4 DC produced IL-10 and IL-6, but no IL-12p70, and were resistant to further maturation. FL DC produced IL-12p70, IFN-alpha/beta, IL-10 and IL-6 and underwent maturation. Repeated stimulation of T cells with GM+IL-4 DC inhibited proliferation, cytokine production and induced early T cell apoptosis. FL DC-activated T cells produced large amounts of IFN-gamma/IL-10 and exhibited late T cell apoptosis/necrosis. In vivo, GM+IL-4 DC induced alloAg-specific hyporesponsiveness following T cell restimulation. These results demonstrate that GM+IL-4 DC display intrinsic regulatory properties, inducing passive-cell-death in T cells with potential for inactivation/regulation of alloreactive T cells in transplantation.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Antibodies, Monoclonal / pharmacology
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Antigen-Presenting Cells / drug effects
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Antigen-Presenting Cells / immunology
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Antigens, CD / analysis
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Antigens, CD / metabolism
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Apoptosis / drug effects
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Apoptosis / immunology
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Cell Differentiation / drug effects
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Cell Differentiation / immunology
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Cell Transplantation
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Dendritic Cells / drug effects
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Dendritic Cells / immunology*
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Dendritic Cells / metabolism
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Dinucleoside Phosphates / pharmacology
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Granulocyte-Macrophage Colony-Stimulating Factor / pharmacology*
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Histocompatibility Antigens / analysis
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Immune Tolerance / drug effects
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Immune Tolerance / immunology
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Interferons / metabolism
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Interleukin-4 / pharmacology*
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Isoantigens / immunology
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Lipopolysaccharides / pharmacology
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Lymphocyte Activation / drug effects
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Lymphocyte Activation / immunology
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Male
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Membrane Proteins / pharmacology*
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Rats
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Rats, Inbred ACI
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Rats, Inbred Lew
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Rats, Inbred WF
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Receptors, Antigen, T-Cell / immunology
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T-Lymphocytes / drug effects
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T-Lymphocytes / immunology*
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T-Lymphocytes / metabolism
Substances
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Antibodies, Monoclonal
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Antigens, CD
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Dinucleoside Phosphates
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Histocompatibility Antigens
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Isoantigens
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Lipopolysaccharides
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Membrane Proteins
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Receptors, Antigen, T-Cell
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flt3 ligand protein
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Interleukin-4
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cytidylyl-3'-5'-guanosine
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Granulocyte-Macrophage Colony-Stimulating Factor
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Interferons