Apoptosis in activated T cells: what are the triggers, and what the signal transducers?
At the end of an immune response, apoptosis drastically reduces the numbers of activated T cells. It has been a matter of intense research how this form of apoptosis is regulated and initiated, and a number of proteins have been identified that contribute to this process. The present, widely accepted model assumes that the interplay of pro- and anti -apoptotic Bcl-2 family members determines the onset of activated T cell death, with the BH3-only protein Bim activating pro-apoptotic Bax/Bak. In the search for up-stream signals, factors from other immune cells have been shown to play a role, and the NFkappaB family member Bcl-3 has been implicated as a signalling-intermediate in T cells. Recent work has tested the interrelation of these factors and has suggested that Bcl-3 acts as a regulator of Bim activation, that the induction of apoptosis through Bim can be complemented by its relative Puma, and that the presence of certain cytokines during T cell activation delays the activation of Bim and Puma. Here we discuss these recent insights and provide a view on how the regulation of activated T cell death is achieved and how extrinsic signals may translate into the activation of the apoptotic pathway.
Häcker
Georg
G
Institute for Medical Microbiology, Technische Universität München, Munich, Germany. hacker@lrz.tum.de
Bauer
Anette
A
Villunger
Andreas
A
D000818:Animals; D017209:Apoptosis; D051017:Apoptosis Regulatory Proteins / Q000378:metabolism; D000072224:Bcl-2-Like Protein 11; D018106:CD28 Antigens / Q000378:metabolism; D002453:Cell Cycle; D002460:Cell Line; D045744:Cell Line, Tumor; D006801:Humans; D007107:Immune System; D008213:Lymphocyte Activation; D008565:Membrane Proteins / Q000378:metabolism; D008954:Models, Biological; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D015398:Signal Transduction; D013601:T-Lymphocytes / Q000378:metabolism / Q000473:pathology*; D014158:Transcription, Genetic
D051017:Apoptosis Regulatory Proteins; C000606775:BCL2L11 protein, human; D000072224:Bcl-2-Like Protein 11; D018106:CD28 Antigens; D008565:Membrane Proteins; D011518:Proto-Oncogene Proteins