4-1BB promotes the survival of CD8+ T lymphocytes by increasing expression of Bcl-xL and Bfl-1

J Immunol. 2002 Nov 1;169(9):4882-8. doi: 10.4049/jimmunol.169.9.4882.

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

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • 4-1BB Ligand
  • Animals
  • Antibodies, Monoclonal / metabolism
  • Antigens, CD
  • Apoptosis / immunology*
  • CD8-Positive T-Lymphocytes / cytology*
  • CD8-Positive T-Lymphocytes / immunology*
  • CD8-Positive T-Lymphocytes / metabolism
  • Cell Division / immunology
  • Cell Survival / immunology
  • Chromones / pharmacology
  • Flavonoids / pharmacology
  • Gene Expression Regulation / immunology
  • Ligands
  • Lymphocyte Activation
  • MAP Kinase Kinase Kinase 1*
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Minor Histocompatibility Antigens
  • Morpholines / pharmacology
  • NF-kappa B / metabolism
  • Phosphatidylinositol 3-Kinases / physiology
  • Protein Serine-Threonine Kinases / physiology
  • Proto-Oncogene Proteins c-bcl-2 / antagonists & inhibitors
  • Proto-Oncogene Proteins c-bcl-2 / biosynthesis*
  • Proto-Oncogene Proteins c-bcl-2 / genetics
  • Pyrrolidines / pharmacology
  • Receptors, Nerve Growth Factor / antagonists & inhibitors
  • Receptors, Nerve Growth Factor / immunology
  • Receptors, Nerve Growth Factor / metabolism
  • Receptors, Nerve Growth Factor / physiology*
  • Receptors, Tumor Necrosis Factor / antagonists & inhibitors
  • Receptors, Tumor Necrosis Factor / immunology
  • Receptors, Tumor Necrosis Factor / metabolism
  • Receptors, Tumor Necrosis Factor / physiology*
  • Signal Transduction / immunology
  • Thiocarbamates / pharmacology
  • Tumor Necrosis Factor Receptor Superfamily, Member 9
  • Tumor Necrosis Factor-alpha / physiology
  • Up-Regulation / immunology
  • bcl-X Protein

Substances

  • 4-1BB Ligand
  • Antibodies, Monoclonal
  • Antigens, CD
  • BCL2-related protein A1
  • Bcl2l1 protein, mouse
  • Chromones
  • Flavonoids
  • Ligands
  • Minor Histocompatibility Antigens
  • Morpholines
  • NF-kappa B
  • Proto-Oncogene Proteins c-bcl-2
  • Pyrrolidines
  • Receptors, Nerve Growth Factor
  • Receptors, Tumor Necrosis Factor
  • Thiocarbamates
  • Tnfrsf9 protein, mouse
  • Tnfsf9 protein, mouse
  • Tumor Necrosis Factor Receptor Superfamily, Member 9
  • Tumor Necrosis Factor-alpha
  • bcl-X Protein
  • pyrrolidine dithiocarbamic acid
  • 2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one
  • Protein Serine-Threonine Kinases
  • MAP Kinase Kinase Kinase 1
  • Map3k1 protein, mouse
  • 2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one