Antigen-mediated T cell expansion regulated by parallel pathways of death.
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.
Ch'en
Irene L
IL
Division of Biological Sciences and Department of Cellular and Molecular Medicine, University of California, San Diego, CA 92093, USA.
Beisner
Daniel R
DR
Degterev
Alexei
A
Lynch
Candace
C
Yuan
Junying
J
Hoffmann
Alexander
A
Hedrick
Stephen M
SM
D019264:Adoptive Transfer; D000818:Animals; D053181:Caspase 8 / Q000235:genetics / Q000276:immunology*; D003433:Crosses, Genetic; D005434:Flow Cytometry; D020868:Gene Silencing; D051379:Mice; D008810:Mice, Inbred C57BL; D016328:NF-kappa B / Q000235:genetics / Q000276:immunology*; D009336:Necrosis / Q000276:immunology*; D053422:Receptor-Interacting Protein Serine-Threonine Kinases / Q000235:genetics / Q000276:immunology*; D013601:T-Lymphocytes / Q000502:physiology* / Q000821:virology
D016328:NF-kappa B; D053422:Receptor-Interacting Protein Serine-Threonine Kinases; C506251:Ripk1 protein, mouse; D053181:Caspase 8