Actin integrity is indispensable for CD95/Fas-induced apoptosis of HIV-specific CD8+ T cells.
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.
Petrovas
Constantinos
C
Department of Microbiology and Immunology, Institute for Molecular Medicine and Infectious Disease, Drexel University College of Medicine, Drexel University, 2900 Queen Lane, Philadelphia, PA 19129, USA.
Mueller
Yvonne M
YM
Yang
Guibin
G
Altork
Susan R
SR
Jacobson
Jeffrey M
JM
Pitsakis
Peter G
PG
Mounzer
Karam C
KC
Altman
John D
JD
Katsikis
Peter D
PD
D000199:Actins / Q000378:metabolism*; D017304:Annexin A5 / Q000378:metabolism; D017209:Apoptosis / Q000187:drug effects; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology* / Q000187:drug effects / Q000201:enzymology / Q000821:virology*; D053181:Caspase 8 / Q000378:metabolism; D002454:Cell Differentiation / Q000187:drug effects; D002469:Cell Separation; D015638:Cytochalasin D / Q000494:pharmacology; D004247:DNA / Q000378:metabolism; D004789:Enzyme Activation / Q000187:drug effects; D006678:HIV / Q000276:immunology*; D006801:Humans; D007156:Immunologic Memory / Q000187:drug effects / Q000276:immunology; D019169:Jurkat Cells; D008213:Lymphocyte Activation / Q000187:drug effects / Q000276:immunology; D019014:fas Receptor / Q000276:immunology*
D000199:Actins; D017304:Annexin A5; D019014:fas Receptor; D015638:Cytochalasin D; D004247:DNA; D053181:Caspase 8