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

2008; National Academy of Sciences; Volume: 105; Issue: 45 Linguagem: Inglês

10.1073/pnas.0808043105

1091-6490

Irene L. Ch’en, Daniel R. Beisner, Alexei Degterev, Candace Lynch, Junying Yuan, Alexander Hoffmann, Stephen Μ. Hedrick,

interferon and immune responses

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 NFκB 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, NFκB, and Ripk1, reveals two forms of cell death that can regulate virus-specific T cell expansion.