Abstract
DcR3/TR6 is a secreted protein belonging to the TNFR family. It binds to Fas ligand, LIGHT, and TL1A, all of which are TNF family members. LIGHT is expressed on activated T cells. Its known receptors are TR2 and LTbetaR on the cell surface, and TR6 in solution. In the present study, we report soluble TR6-Fc or solid-phase TR6-Fc costimulated proliferation, lymphokine production, and cytotoxicity of human T cells in the presence of TCR ligation. These costimulating effects were blocked by soluble LIGHT but not by soluble Fas-Fc. TR6-Fc could also effectively costimulate gld/gld mouse T cells. We further demonstrated that TR6 bound to both Th1 and Th2 cells, according to flow cytometry, and that the association was inhibited by soluble LIGHT. Cross-linking Th1 and Th2 cells with solid-phase TR6-Fc along with a suboptimal concentration of anti-CD3 enhanced proliferation of both Th1 and Th2 cells, and augmented Th1 but not Th2 lymphokine production. These data suggest that TR6 delivers costimulation through its ligand(s) on the T cell surface, and at least the major part of such costimulation is via LIGHT.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Adjuvants, Immunologic / metabolism
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Adjuvants, Immunologic / physiology
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Adult
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Animals
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Cell Differentiation / immunology
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Cells, Cultured
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Dose-Response Relationship, Immunologic
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Humans
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Leukocytes, Mononuclear / cytology
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Leukocytes, Mononuclear / immunology
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Leukocytes, Mononuclear / metabolism
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Ligands
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Lymphocyte Activation / immunology*
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Lymphokines / biosynthesis
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Membrane Glycoproteins / metabolism
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Membrane Glycoproteins / physiology*
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Membrane Proteins / biosynthesis
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Membrane Proteins / metabolism
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Membrane Proteins / physiology*
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Mice
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Mice, Inbred C57BL
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Mitogens / pharmacology
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Protein Binding / immunology
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Receptors, Cell Surface / metabolism
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Receptors, Cell Surface / physiology*
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Receptors, Tumor Necrosis Factor
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Receptors, Tumor Necrosis Factor, Member 6b
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Signal Transduction / immunology*
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Solubility
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T-Lymphocyte Subsets / cytology
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T-Lymphocyte Subsets / immunology*
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T-Lymphocyte Subsets / metabolism*
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T-Lymphocytes, Cytotoxic / cytology
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Th1 Cells / immunology
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Th1 Cells / metabolism
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Th2 Cells / immunology
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Th2 Cells / metabolism
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Tumor Necrosis Factor Ligand Superfamily Member 14
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Tumor Necrosis Factor-alpha / biosynthesis
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Tumor Necrosis Factor-alpha / metabolism
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Tumor Necrosis Factor-alpha / physiology*
Substances
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Adjuvants, Immunologic
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Ligands
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Lymphokines
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Membrane Glycoproteins
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Membrane Proteins
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Mitogens
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Receptors, Cell Surface
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Receptors, Tumor Necrosis Factor
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Receptors, Tumor Necrosis Factor, Member 6b
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TNFRSF6B protein, human
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TNFSF14 protein, human
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Tnfsf14 protein, mouse
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Tumor Necrosis Factor Ligand Superfamily Member 14
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Tumor Necrosis Factor-alpha