Abstract
4-1BB, a T cell costimulatory receptor, prolongs CD8(+) T cell survival. In these studies, 4-1BB stimulation was shown to increase expression of the antiapoptotic genes bcl-x(L) and bfl-1 via 4-1BB-mediated NF-kappaB activation. This signaling pathway was specifically inhibited by PDTC and was different from the pathways that enhanced CD8(+) T cell proliferation. The results suggest a role for the antiapoptotic activities of Bcl-x(L) and Bfl-1 proteins in 4-1BB-mediated CD8(+) T cell survival in vivo.
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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4-1BB Ligand
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Animals
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Antibodies, Monoclonal / metabolism
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Antigens, CD
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Apoptosis / immunology*
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CD8-Positive T-Lymphocytes / cytology*
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CD8-Positive T-Lymphocytes / immunology*
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CD8-Positive T-Lymphocytes / metabolism
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Cell Division / immunology
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Cell Survival / immunology
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Chromones / pharmacology
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Flavonoids / pharmacology
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Gene Expression Regulation / immunology
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Ligands
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Lymphocyte Activation
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MAP Kinase Kinase Kinase 1*
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Male
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Mice
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Mice, Inbred BALB C
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Minor Histocompatibility Antigens
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Morpholines / pharmacology
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NF-kappa B / metabolism
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Phosphatidylinositol 3-Kinases / physiology
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Protein Serine-Threonine Kinases / physiology
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Proto-Oncogene Proteins c-bcl-2 / antagonists & inhibitors
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Proto-Oncogene Proteins c-bcl-2 / biosynthesis*
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Proto-Oncogene Proteins c-bcl-2 / genetics
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Pyrrolidines / pharmacology
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Receptors, Nerve Growth Factor / antagonists & inhibitors
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Receptors, Nerve Growth Factor / immunology
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Receptors, Nerve Growth Factor / metabolism
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Receptors, Nerve Growth Factor / physiology*
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Receptors, Tumor Necrosis Factor / antagonists & inhibitors
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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 / physiology*
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Signal Transduction / immunology
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Thiocarbamates / pharmacology
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Tumor Necrosis Factor Receptor Superfamily, Member 9
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Tumor Necrosis Factor-alpha / physiology
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Up-Regulation / immunology
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bcl-X Protein
Substances
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4-1BB Ligand
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Antibodies, Monoclonal
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Antigens, CD
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BCL2-related protein A1
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Bcl2l1 protein, mouse
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Chromones
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Flavonoids
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Ligands
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Minor Histocompatibility Antigens
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Morpholines
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NF-kappa B
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Proto-Oncogene Proteins c-bcl-2
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Pyrrolidines
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Receptors, Nerve Growth Factor
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Receptors, Tumor Necrosis Factor
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Thiocarbamates
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Tnfrsf9 protein, mouse
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Tnfsf9 protein, mouse
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Tumor Necrosis Factor Receptor Superfamily, Member 9
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Tumor Necrosis Factor-alpha
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bcl-X Protein
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pyrrolidine dithiocarbamic acid
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2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one
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Protein Serine-Threonine Kinases
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MAP Kinase Kinase Kinase 1
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Map3k1 protein, mouse
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2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one