Abstract
LIGHT was recently described as a member of the tumor necrosis factor (TNF) 'superfamily'. We have isolated a mouse homolog of human LIGHT and investigated its immunoregulatory functions in vitro and in vivo. LIGHT has potent, CD28-independent co-stimulatory activity leading to T-cell growth and secretion of gamma interferon and granulocyte-macrophage colony-stimulating factor. Gene transfer of LIGHT induced an antigen-specific cytolytic T-cell response and therapeutic immunity against established mouse P815 tumor. In contrast, blockade of LIGHT by administration of soluble receptor or antibody led to decreased cell-mediated immunity and ameliorated graft-versus-host disease. Our studies identify a previously unknown T-cell co-stimulatory pathway as a potential therapeutic target.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Amino Acid Sequence
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Animals
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CD18 Antigens / immunology
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Cell Line
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Cloning, Molecular
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Graft vs Host Disease / immunology*
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Granulocyte-Macrophage Colony-Stimulating Factor / biosynthesis
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Humans
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Immunity, Cellular
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Interferon-gamma / biosynthesis
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Membrane Proteins / chemistry
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Membrane Proteins / genetics
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Membrane Proteins / immunology*
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Mice
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Models, Biological
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Molecular Sequence Data
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Recombinant Fusion Proteins / biosynthesis
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Recombinant Proteins / chemistry
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Recombinant Proteins / immunology
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Reverse Transcriptase Polymerase Chain Reaction
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Sequence Alignment
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Sequence Homology, Amino Acid
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T-Lymphocytes / immunology*
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Transfection
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Tumor Cells, Cultured
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Tumor Necrosis Factor Ligand Superfamily Member 14
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Tumor Necrosis Factor-alpha / chemistry
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Tumor Necrosis Factor-alpha / genetics
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Tumor Necrosis Factor-alpha / immunology*
Substances
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CD18 Antigens
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Membrane Proteins
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Recombinant Fusion Proteins
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Recombinant Proteins
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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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Interferon-gamma
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Granulocyte-Macrophage Colony-Stimulating Factor