Abstract
TR6 (DcR3) is a new member of the TNF receptor (TNFR) family that lacks a transmembrane domain in its sequence, indicating that it is a secreted molecule. TR6 can bind to FasL and prevent FasL-induced apoptosis; it can also associate with LIGHT, another TNF family member. The role of TR6 in immune responses was investigated in this study. According to flow cytometry, recombinant human TR6-Fc binds to human LIGHT expressed on 293 cells or on activated human T cells and competes with the LIGHT receptor TR2 for the binding to LIGHT on these cells. Human TR6 could cross-react with mouse LIGHT in immunoprecipitation. TR6-Fc also downregulates cytotoxic T lymphocyte activity in vitro and graft-versus-host responses in mice. Moreover, TR6-Fc modulates lymphokine production by alloantigen-stimulated mouse T cells. TR6-Fc ameliorated rejection response to mouse heart allograft. These results indicate that TR6 can dampen T-cell responses to alloantigens. Such regulatory effects of TR6 probably occur via interference with interaction between pairs of related TNF and TNFR family members, LIGHT/TR2 being one of the possible candidate pairs.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Cell Line
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Female
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Flow Cytometry
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Granulocyte-Macrophage Colony-Stimulating Factor / metabolism
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Heart Transplantation / physiology
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Humans
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Immunoblotting
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Interferon-alpha / metabolism
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Interleukin-10 / metabolism
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Interleukin-6 / metabolism
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Isoantigens / immunology*
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Isoantigens / metabolism
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Membrane Glycoproteins*
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Membrane Proteins / metabolism
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Mice
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Mice, Inbred BALB C
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Mice, Inbred C57BL
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Mice, Transgenic
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Precipitin Tests
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Receptors, Cell Surface / immunology*
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Receptors, Cell Surface / metabolism
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Receptors, Tumor Necrosis Factor / immunology
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Receptors, Tumor Necrosis Factor / metabolism*
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Receptors, Tumor Necrosis Factor, Member 6b
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Recombinant Fusion Proteins / genetics
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Recombinant Fusion Proteins / metabolism
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Spleen / cytology
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Spleen / metabolism
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T-Lymphocytes / immunology*
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T-Lymphocytes / physiology
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Tumor Necrosis Factor Ligand Superfamily Member 14
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Tumor Necrosis Factor-alpha / metabolism
Substances
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Interferon-alpha
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Interleukin-6
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Isoantigens
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Membrane Glycoproteins
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Membrane Proteins
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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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Recombinant Fusion Proteins
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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
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Interleukin-10
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Granulocyte-Macrophage Colony-Stimulating Factor