How T lymphocytes switch between life and death.
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.
Arnold
Rüdiger
R
Tumor Immunology Program, German Cancer Research Center, Heidelberg, Germany. r.arnold@dkfz.de
Brenner
Dirk
D
Becker
Mareike
M
Frey
Christian R
CR
Krammer
Peter H
PH
D000818:Animals; D017209:Apoptosis / Q000276:immunology*; D002470:Cell Survival / Q000276:immunology; D006801:Humans; D013601:T-Lymphocytes / Q000166:cytology* / Q000276:immunology*