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Actin integrity is indispensable for CD95/Fas-induced apoptosis of HIV-specific CD8(+) T cells
Journal article   Peer reviewed

Actin integrity is indispensable for CD95/Fas-induced apoptosis of HIV-specific CD8(+) T cells

Constantinos Petrovas, Yvonne M. Mueller, Guibin Yang, Susan R. Altork, Jeffrey M. Jacobson, Peter G. Pitsakis, Karam C. Mounzer, John D. Altman and Peter D. Katsikis
Apoptosis (London), v 12(12), pp 2175-2186
01 Dec 2007
PMID: 17891455

Abstract

Biochemistry & Molecular Biology Cell Biology Life Sciences & Biomedicine Science & Technology
We have recently provided data suggesting a potential role for mitochondria and Bcl-2-family molecules in apoptosis sensitivity of HIV-specific CD8(+) T cells. Here, we report on the role of filamentous (F) actin in this process. Disruption of actin by cytochalasin D (cytD) or lantrunculin A remarkably reduced CD95/Fas-induced apoptosis of HIV-specific CD8(+) T cells while their spontaneous apoptosis was unaffected. This inhibition cannot be attributed to changes of CD95/Fas distribution or levels in these cells. Furthermore, cytD treatment reduced CD95/Fas-induced apoptosis of CD8(+) T cells from HIV+ patients independently of their differentiation status. CD95/Fas-induced apoptosis of both CD38(+) and CD38(-) HIV-specific CD8(+) T cells was inhibited by cytD treatment indicating that actin mediates this apoptotic process independently of the activation level of these cells. CytD was found to reduce the activation of caspase-8 induced by short treatment of purified CD8(+) T cells from HIV+ patients with anti-CD95/Fas. Our data reveal actin as a critical mediator of HIV-specific CD8(+) T cell apoptosis; further analysis of the molecular mechanisms governing this process may potentially contribute to design new therapies targeting the enhancement of the immune system in HIV infection.

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Collaboration types
Domestic collaboration
Web of Science research areas
Biochemistry & Molecular Biology
Cell Biology
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