title: How T lymphocytes switch between life and death.
abstract: While insufficient cell death of activated T cells can result in autoimmune disorders, elimination of too many T cells can lead to immunodeficiency. Therefore, T lymphocyte fate is highly regulated and requires that cells can switch from an apoptosis-resistant towards an apoptosis-sensitive state. This switch is tightly controlled by various effector molecules. Basically, two separate pathways control the fate of antigen-activated T cells: activation-induced cell death (AICD) and activated T cell autonomous death (ACAD). Autoreactive T lymphocytes are eliminated by restimulation via their T cell receptor (TCR) and undergo AICD involving death receptors (extrinsic pathway). In contrast, ACAD can lead to T cell deletion without TCR restimulation, and is determined by the ratio between anti- and pro-apoptotic Bcl-2 family members at the mitochondria (intrinsic pathway). While the extrinsic and the intrinsic pathway lead to caspase activation, non-caspase proteases (e.g., cathepsins) can be released by the lysosomes and might contribute to AICD as well as to ACAD. Activated T cells poses cell death escape mechanisms which are needed for survival of (memory) T cells, but are deleterious for autoimmune disorders or progression of T cell lymphomas.
authors.affiliation: Tumor Immunology Program, German Cancer Research Center, Heidelberg, Germany. r.arnold@dkfz.de
authors.forename: Rüdiger
authors.initials: R
authors.lastname: Arnold
authors.forename: Dirk
authors.initials: D
authors.lastname: Brenner
authors.forename: Mareike
authors.initials: M
authors.lastname: Becker
authors.forename: Christian R
authors.initials: CR
authors.lastname: Frey
authors.forename: Peter H
authors.initials: PH
authors.lastname: Krammer
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000276:immunology*; D002470:Cell Survival / Q000276:immunology; D006801:Humans; D013601:T-Lymphocytes / Q000166:cytology* / Q000276:immunology*