title: Regulation of oxidative stress responses by ataxia-telangiectasia mutated is required for T cell proliferation.
abstract: Mutations in the gene encoding ataxia-telangiectasia (A-T) mutated (Atm) cause the disease A-T, characterized by immunodeficiency, the molecular basis of which is not known. Following stimulation through the TCR, Atm-deficient T cells and normal T cells in which Atm is inhibited undergo apoptosis rather than proliferation. Apoptosis is prevented by scavenging reactive oxygen species (ROS) during activation. Atm therefore plays a critical role in T cell proliferation by regulating responses to ROS generated following T cell activation. The inability of Atm-deficient T cells to control responses to ROS is therefore the molecular basis of immunodeficiency associated with A-T.
authors.affiliation: Transplantation Research Center, Renal Division, Brigham and Women's Hospital and Children's Hospital Boston, Harvard Medical School, Boston, MA 02115, USA.
authors.forename: Jessamyn
authors.initials: J
authors.lastname: Bagley
authors.forename: Gyanesh
authors.initials: G
authors.lastname: Singh
authors.forename: John
authors.initials: J
authors.lastname: Iacomini
mesh_terms: D000818:Animals; D017209:Apoptosis; D064007:Ataxia Telangiectasia Mutated Proteins; D018106:CD28 Antigens / Q000502:physiology; D017252:CD3 Complex / Q000502:physiology; D018797:Cell Cycle Proteins / Q000502:physiology*; D004268:DNA-Binding Proteins / Q000502:physiology*; D008213:Lymphocyte Activation; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018384:Oxidative Stress; D017346:Protein Serine-Threonine Kinases / Q000502:physiology*; D017382:Reactive Oxygen Species / Q000378:metabolism; D011948:Receptors, Antigen, T-Cell / Q000502:physiology; D013601:T-Lymphocytes / Q000276:immunology*; D025521:Tumor Suppressor Proteins / Q000502:physiology*
chemical_list: D018106:CD28 Antigens; D017252:CD3 Complex; D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; D017382:Reactive Oxygen Species; D011948:Receptors, Antigen, T-Cell; D025521:Tumor Suppressor Proteins; D064007:Ataxia Telangiectasia Mutated Proteins; C576325:Atm protein, mouse; D017346:Protein Serine-Threonine Kinases