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PMID: 18981423 Published · ppublish English Comparative Study Journal Article Research Support, N.I.H., Extramural

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

Proceedings of the National Academy of Sciences of the United States of America ·Vol. 105 ·No. 45 ·2008-11-11 ·Pages 17463-8

Ch'en IL, Beisner DR, Degterev A, Lynch C, Yuan J, Hoffmann A, Hedrick SM

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.

MeSH Terms
Adoptive Transfer Animals Caspase 8/genetics,immunology Crosses, Genetic Flow Cytometry Gene Silencing Mice Mice, Inbred C57BL NF-kappa B/genetics,immunology Necrosis/immunology Receptor-Interacting Protein Serine-Threonine Kinases/genetics,immunology T-Lymphocytes/physiology,virology
Chemicals
NF-kappa B Receptor-Interacting Protein Serine-Threonine Kinases Ripk1 protein, mouse Caspase 8
Authors & Affiliations
7 authors, click to expand affiliations / ORCID
Ch'en Irene L
Division of Biological Sciences and Department of Cellular and Molecular Medicine, University of California, San Diego, CA 92093, USA.
Beisner Daniel R
Degterev Alexei
Lynch Candace
Yuan Junying
Hoffmann Alexander
Hedrick Stephen M
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Article Info
Journal
Proceedings of the National Academy of Sciences of the United States of America
Abbr.
Proc Natl Acad Sci U S A
ISSN
1091-6490
DOI
10.1073/pnas.0808043105
Published
2008-11-11
Epub
2008-00-03
Pages
17463-8
Language
English
Region
United States
NLM ID
7505876
PMCID
PMC2582294
Subset
IM
Grants
NIAID NIH HHS · R01 AI037988 · United States
NIDDK NIH HHS · T32 DK007233 · United States
NIGMS NIH HHS · R01 GM071573-03 · United States
NIDDK NIH HHS · T32DK007233 · United States
NIAID NIH HHS · AI037988 · United States
NIGMS NIH HHS · R01 GM071573 · United States
External Links
PubMed source DOI: 10.1073/pnas.0808043105 PMC Full Text View journal details
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