Resistance to apoptosis in HIV-infected CD4+ T lymphocytes is mediated by macrophages: role for Nef and immune activation in viral persistence.

Mahlknecht, U; Deng, C; Lu, M C; Greenough, T C; Sullivan, J L; O'Brien, W A; Herbein, G

Mahlknecht, U; Deng, C; Lu, M C; Greenough, T C; Sullivan, J L; O'Brien, W A; Herbein, G.

Afiliación

Mahlknecht U; Department of Hematology/Oncology, University of Frankfurt, Frankfurt am Main, Germany.

J Immunol ; 165(11): 6437-46, 2000 Dec 01.

Article en En | MEDLINE | ID: mdl-11086083

RESUMEN

Apoptosis or programmed cell death may play a critical role in AIDS pathogenesis through depletion of both CD4(+) and CD8(+) T lymphocytes. Using a reporter virus, a recombinant HIV infectious clone expressing the green fluorescent protein (GFP), apoptosis was measured in productively infected CD4(+) T lymphocytes, in the presence and absence of autologous macrophages. The presence of macrophages in the culture increased the frequency of nonapoptotic GFP-positive productively infected CD4(+) T lymphocytes. The appearance of nonapoptotic productively infected CD4(+) T lymphocytes in the culture required intercellular contacts between macrophages and PBLs and the expression of the HIV Nef protein. The presence of macrophages did not reduce apoptosis when CD4(+) T lymphocytes were infected with a GFP-tagged virus deleted for the nef gene. TNF-alpha (TNF) expressed on the surface of macrophages prevented apoptosis in nef-expressing, productively infected CD4(+) T lymphocytes. Similarly, following TNF stimulation, apoptosis was diminished in Jurkat T cells transfected with a nef-expressing plasmid. TNF stimulation of nef-expressing Jurkat T cells resulted in NF-kappaB hyperactivation, which has been shown to deliver anti-apoptotic signals. Our results indicate that intercellular contacts with macrophages increase the rate of productively infected nonapoptotic CD4(+) T lymphocytes. The survival of productively infected CD4(+) T lymphocytes requires Nef expression as well as activation by TNF expressed on the surface of macrophages and might participate in the formation and maintenance of viral reservoirs in HIV-infected persons.

Asunto(s)

Apoptosis/inmunología; Linfocitos T CD4-Positivos/inmunología; Linfocitos T CD4-Positivos/virología; Productos del Gen nef/fisiología; VIH-1/inmunología; Activación de Linfocitos/inmunología; Macrófagos/inmunología; Latencia del Virus/inmunología; Animales; Apoptosis/genética; Linfocitos T CD4-Positivos/citología; Linfocitos T CD4-Positivos/metabolismo; Células CHO; Comunicación Celular/genética; Comunicación Celular/inmunología; Células Cultivadas; Cricetinae; Productos del Gen nef/biosíntesis; Productos del Gen nef/genética; Proteínas Fluorescentes Verdes; VIH-1/genética; Humanos; Inmunidad Innata; Células Jurkat; Proteínas Luminiscentes/genética; Activación de Linfocitos/genética; FN-kappa B/genética; FN-kappa B/metabolismo; Transfección; Factor de Necrosis Tumoral alfa/inmunología; Latencia del Virus/genética; Productos del Gen nef del Virus de la Inmunodeficiencia Humana

Buscar en Google

Añadir a Mi BVS

Imprimir

XML

PubMed Links

Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Activación de Linfocitos / Linfocitos T CD4-Positivos / Productos del Gen nef / VIH-1 / Apoptosis / Latencia del Virus / Macrófagos Límite: Animals / Humans Idioma: En Revista: J Immunol Año: 2000 Tipo del documento: Article País de afiliación: Alemania Pais de publicación: Estados Unidos

Buscar en Google

Añadir a Mi BVS

Imprimir

XML

PubMed Links