Reactive oxygen species regulate activation-induced T cell apoptosis

Immunity. 1999 Jun;10(6):735-44. doi: 10.1016/s1074-7613(00)80072-2.

Abstract

Reactive oxygen species (ROS) mediate apoptosis in a number of cell types. We studied the role that ROS play in activated T cell apoptosis by activating T cells in vivo and then culturing them for a short time. Activated T cells died independently of Fas and TNF alpha. Their death was characterized by rapid loss of mitochondrial transmembrane potential (delta psi(m)), caspase-dependent DNA fragmentation, and superoxide generation. A superoxide dismutase mimetic, Mn (III) tetrakis (5, 10, 15, 20-benzoic acid) porphyrin (MnTBAP), protected T cells from superoxide generation, caspase-dependent DNA loss, loss of delta psi(m), and cell death. These results indicate that ROS can regulate signals involved in caspase activation and apoptosis and may contribute to peripheral T cell deletion.

Publication types

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

MeSH terms

  • Animals
  • Apoptosis / drug effects
  • Apoptosis / immunology*
  • Caspases / metabolism
  • Caspases / physiology
  • Enzyme Activation / drug effects
  • Enzyme Activation / immunology
  • Female
  • Free Radical Scavengers / pharmacology
  • Leukemia L1210
  • Lymphocyte Activation* / drug effects
  • Manganese / pharmacology
  • Membrane Potentials / drug effects
  • Membrane Potentials / immunology
  • Metalloporphyrins / pharmacology
  • Mice
  • Mice, Inbred C57BL
  • Mitochondria / drug effects
  • Mitochondria / physiology
  • Reactive Oxygen Species / physiology*
  • Superantigens / pharmacology
  • T-Lymphocytes / physiology*
  • Tumor Necrosis Factor-alpha / pharmacology
  • fas Receptor / pharmacology

Substances

  • Free Radical Scavengers
  • Metalloporphyrins
  • Reactive Oxygen Species
  • Superantigens
  • Tumor Necrosis Factor-alpha
  • fas Receptor
  • manganese(III)-tetrakis(4-benzoic acid)porphyrin
  • Manganese
  • Caspases