title: Inhibition of activation-induced death in T cell hybridomas by thiol antioxidants: oxidative stress as a mediator of apoptosis.
abstract: N-Acetylcysteine (NAC) is a well established thiol antioxidant which, after uptake, deacylation and conversion to glutathione functions as both a redox buffer and a reactive oxygen intermediate scavenger. We report here that NAC completely blocks activation induced death and associated DNA fragmentation of myelin basic protein (MBP) specific T cell hybridomas. Conversely, NAC had very little effect on the antigen driven proliferation of a MBP specific T cell line similar to that from which the hybridomas were derived. NAC displayed an analogous absolute inhibition of mitogen mediated activation induced death, even if added up to 3 h post activation. Although glutathione was as efficient as NAC at blocking activation induced death, dithiothreitol displayed minimal inhibition while L-cysteine had no effect at all. The observation that certain thiol antioxidants such as NAC and glutathione can completely block the activation induced death of T cell hybridomas implicates redox regulation in this process.
authors.affiliation: Department of Microbiology and Immunology, East Carolina University, School of Medicine, Greenville, NC 27858.
authors.forename: P A
authors.initials: PA
authors.lastname: Sandstrom
authors.forename: M D
authors.initials: MD
authors.lastname: Mannie
authors.forename: T M
authors.initials: TM
authors.lastname: Buttke
mesh_terms: D000111:Acetylcysteine / Q000494:pharmacology*; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology*; D002478:Cells, Cultured; D006825:Hybridomas / Q000166:cytology* / Q000187:drug effects / Q000276:immunology; D037102:Lectins; D008213:Lymphocyte Activation; D004676:Myelin Basic Protein / Q000276:immunology / Q000494:pharmacology; D010084:Oxidation-Reduction; D051381:Rats; D011917:Rats, Inbred Lew; D013312:Stress, Physiological; D013601:T-Lymphocytes / Q000166:cytology* / Q000187:drug effects / Q000276:immunology; D013945:Thymoma; D014407:Tumor Cells, Cultured
chemical_list: D000975:Antioxidants; D037102:Lectins; D004676:Myelin Basic Protein; D000111:Acetylcysteine