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Antigen-mediated T cell expansion regulated by parallel pathways of death.


ABSTRACT: T cells enigmatically require caspase-8, an inducer of apoptosis, for antigen-driven expansion and effective antiviral responses, and yet the pathways responsible for this effect have been elusive. A defect in caspase-8 expression does not affect progression through the cell cycle but causes an abnormally high rate of cell death that is distinct from apoptosis and does not involve a loss of NFkappaB activation. Instead, antigen or mitogen activated Casp8-deficient T cells exhibit an alternative type of cell death similar to programmed necrosis that depends on receptor interacting protein (Ripk1). The selective genetic ablation of caspase-8, NFkappaB, and Ripk1, reveals two forms of cell death that can regulate virus-specific T cell expansion.

SUBMITTER: Ch'en IL 

PROVIDER: S-EPMC2582294 | biostudies-literature | 2008 Nov

REPOSITORIES: biostudies-literature

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Antigen-mediated T cell expansion regulated by parallel pathways of death.

Ch'en Irene L IL   Beisner Daniel R DR   Degterev Alexei A   Lynch Candace C   Yuan Junying J   Hoffmann Alexander A   Hedrick Stephen M SM  

Proceedings of the National Academy of Sciences of the United States of America 20081103 45


T cells enigmatically require caspase-8, an inducer of apoptosis, for antigen-driven expansion and effective antiviral responses, and yet the pathways responsible for this effect have been elusive. A defect in caspase-8 expression does not affect progression through the cell cycle but causes an abnormally high rate of cell death that is distinct from apoptosis and does not involve a loss of NFkappaB activation. Instead, antigen or mitogen activated Casp8-deficient T cells exhibit an alternative  ...[more]

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