RESUMEN
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.
Asunto(s)
Actinas/metabolismo , Apoptosis , Linfocitos T CD8-positivos/citología , Linfocitos T CD8-positivos/virología , VIH/inmunología , Receptor fas/inmunología , Anexina A5/metabolismo , Apoptosis/efectos de los fármacos , Linfocitos T CD8-positivos/efectos de los fármacos , Linfocitos T CD8-positivos/enzimología , Caspasa 8/metabolismo , Diferenciación Celular/efectos de los fármacos , Separación Celular , Citocalasina D/farmacología , ADN/metabolismo , Activación Enzimática/efectos de los fármacos , Humanos , Memoria Inmunológica/efectos de los fármacos , Memoria Inmunológica/inmunología , Células Jurkat , Activación de Linfocitos/efectos de los fármacos , Activación de Linfocitos/inmunologíaRESUMEN
Although the production of extended-spectrum beta-lactamases (ESBLs) by Klebsiella pneumoniae and Escherichia coli is an emerging problem, limited data are available regarding the frequency of ESBL production in other organisms. We provide the only description of regional occurrence of SHV-7 in Enterobacteriaceae other than E. coli or K. pneumoniae in the United States, and we emphasize that, among Enterobacter cloacae strains, not all resistance to extended-spectrum cephalosporins is the result of hyperproduction of AmpC beta-lactamase.