Abstract
A panel of monoclonal antibodies specific for CD27 ligand (CD70), CD30 ligand (CD153), CD134 ligand (OX40L), and CD137 ligand (4-1BBL) were screened in vivo for their ability to affect the control of Mycobacterium avium infection in C57Bl/6 mice. Only the blocking of CD153 led to increased mycobacterial burdens. We then used CD30-deficient mice and found an increase in the proliferation of two strains of M. avium in these mice as compared with control animals. The increased mycobacterial growth was associated with decreased T cell expansion and reduced interferon-gamma (IFN-gamma) responses as a result of reduced polarization of the antigen-specific, IFN-gamma-producing T cells. At late times but not early in infection, the lymphoid cuff surrounding granulomas was depleted in the CD30-deficient animals. This report expands our knowledge about tumor necrosis factor superfamily members involved in the immune responses to mycobacterial infection by identifying CD30-CD153 interactions as required for optimal immune control of M. avium infection.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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4-1BB Ligand
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Animals
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Antibodies, Monoclonal / pharmacology
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Antigens, CD / immunology
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CD27 Ligand
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CD30 Ligand
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Cell Division / immunology
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Cells, Cultured
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Disease Models, Animal
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Female
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Humans
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Immunity, Cellular / immunology*
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Interferon-gamma / immunology
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Ki-1 Antigen / genetics
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Ki-1 Antigen / immunology*
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Membrane Glycoproteins / antagonists & inhibitors
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Membrane Glycoproteins / immunology*
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Membrane Proteins / antagonists & inhibitors
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Membrane Proteins / immunology
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Mice
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Mice, Inbred C57BL
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Mycobacterium avium / growth & development
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Mycobacterium avium / immunology*
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Mycobacterium avium / pathogenicity
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OX40 Ligand
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Receptors, Nerve Growth Factor / immunology
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Receptors, OX40
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Receptors, Tumor Necrosis Factor / immunology
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T-Lymphocytes / immunology
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Tuberculosis / genetics
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Tuberculosis / immunology*
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Tuberculosis / microbiology
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Tumor Necrosis Factor Receptor Superfamily, Member 7 / immunology
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Tumor Necrosis Factor Receptor Superfamily, Member 9
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Tumor Necrosis Factor-alpha / antagonists & inhibitors
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Tumor Necrosis Factor-alpha / immunology
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Tumor Necrosis Factors
Substances
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4-1BB Ligand
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Antibodies, Monoclonal
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Antigens, CD
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CD27 Ligand
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CD30 Ligand
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CD70 protein, human
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Cd70 protein, mouse
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Ki-1 Antigen
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Membrane Glycoproteins
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Membrane Proteins
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OX40 Ligand
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Receptors, Nerve Growth Factor
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Receptors, OX40
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Receptors, Tumor Necrosis Factor
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TNFRSF4 protein, human
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TNFRSF9 protein, human
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TNFSF4 protein, human
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TNFSF8 protein, human
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TNFSF9 protein, human
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Tnfrsf4 protein, mouse
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Tnfrsf9 protein, mouse
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Tnfsf4 protein, mouse
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Tnfsf8 protein, mouse
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Tnfsf9 protein, mouse
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Tumor Necrosis Factor Receptor Superfamily, Member 7
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Tumor Necrosis Factor Receptor Superfamily, Member 9
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Tumor Necrosis Factor-alpha
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Tumor Necrosis Factors
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Interferon-gamma