Journal
IMMUNITY
Volume 41, Issue 6, Pages 1001-1012Publisher
CELL PRESS
DOI: 10.1016/j.immuni.2014.12.011
Keywords
-
Categories
Funding
- Howard Hughes Medical Institute
- Ragon Institute
- NIH [AI30914, AI105343, AI112521, AI082630, AI095608, HHSN266200500030C]
- Bill and Melinda Gates Foundation
- NIH-funded Center for AIDS Research grant [P30 AI060354]
- NIH Co-Funding and Participating Institute and Center: NIAID
- NIH Co-Funding and Participating Institute and Center: NCI
- NIH Co-Funding and Participating Institute and Center: NICHD
- NIH Co-Funding and Participating Institute and Center: NHLBI
- NIH Co-Funding and Participating Institute and Center: NIDA
- NIH Co-Funding and Participating Institute and Center: NIMH
- NIH Co-Funding and Participating Institute and Center: NIA
- NIH Co-Funding and Participating Institute and Center: FIC
- NIH Co-Funding and Participating Institute and Center: OAR
Ask authors/readers for more resources
Decreased HIV-specific CD8(+) T cell proliferation is a hallmark of chronic infection, but the mechanisms of decline are unclear. We analyzed gene expression profiles from antigen-stimulated HIV-specific CD8(+) T cells from patients with controlled and uncontrolled infection and identified caspase-8 as a correlate of dysfunctional CD8(+) T cell proliferation. Caspase-8 activity was upregulated in HIV-specific CD8(+) T cells from progressors and correlated positively with disease progression and programmed cell death-1 (PD-1) expression, but negatively with proliferation. In addition, progressor cells displayed a decreased ability to upregulate membrane-associated caspase-8 activity and increased necrotic cell death following antigenic stimulation, implicating the programmed cell death pathway necroptosis. In vitro necroptosis blockade rescued HIV-specific CD8(+) T cell proliferation in progressors, as did silencing of necroptosis mediator RIPK3. Thus, chronic stimulation leading to upregulated caspase-8 activity contributes to dysfunctional HIV-specific CD8(+) T cell proliferation through activation of necroptosis and increased cell death.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available