title: Death of CD4+ T cells from lymph nodes during primary SIVmac251 infection predicts the rate of AIDS progression.
abstract: Immunological and virological events that occur during the earliest stages of SIV infection are now considered to have a major impact on subsequent disease progression. In the present study, we demonstrate a clear correlation between progression to AIDS and the rate of in vitro CD4+ (but not CD8+) T cell death in lymph nodes. The dying CD4+ T cells were effector memory T cells, which are critical for the immune response to pathogens. However, there was no correlation between the rate of the viral replication within lymph nodes and the extent of Fas ligand-mediated death, despite the increased sensitivity of CD4+ T cells to death in response to recombinant human Fas ligand. CD4+ T cell death was caspase and apoptosis-inducing factor independent but was clearly associated with mitochondrion damage. Interestingly, higher expression levels of the active form of Bak, a proapoptotic molecule involved in mitochondrial membrane permeabilization, were observed in SIV-infected macaques progressing more rapidly to AIDS. Finally, we demonstrated that the strain of SIV we used requires CCR5 and BOB/GRP15 molecules as coreceptors and caused death of unstimulated noncycling primary CD4+ T cells. Altogether, these results demonstrate that CD4+ T cell death occurring early after SIV infection is a crucial determinant of progression to AIDS and that it is mediated by the intrinsic death pathway.
authors.affiliation: Unité de Physiopathologie des Infections Lentivirales, Institut Pasteur, Paris, France.
authors.forename: Laurence
authors.initials: L
authors.lastname: Viollet
authors.forename: Valérie
authors.initials: V
authors.lastname: Monceaux
authors.forename: Frédéric
authors.initials: F
authors.lastname: Petit
authors.forename: Raphaël
authors.initials: R
authors.lastname: Ho Tsong Fang
authors.forename: Marie-Christine
authors.initials: MC
authors.lastname: Cumont
authors.forename: Bruno
authors.initials: B
authors.lastname: Hurtrel
authors.forename: Jérôme
authors.initials: J
authors.lastname: Estaquier
mesh_terms: D000818:Animals; D051033:Apoptosis Inducing Factor / Q000502:physiology; D015496:CD4-Positive T-Lymphocytes / Q000201:enzymology / Q000473:pathology* / Q000821:virology; D061945:Caspase Inhibitors; D020169:Caspases / Q000378:metabolism / Q000502:physiology; D016923:Cell Death / Q000276:immunology; D002478:Cells, Cultured; D018450:Disease Progression; D008198:Lymph Nodes / Q000276:immunology* / Q000473:pathology* / Q000821:virology; D018655:Lymphocyte Count; D008253:Macaca mulatta; D008564:Membrane Potentials / Q000276:immunology; D051336:Mitochondrial Membranes / Q000201:enzymology / Q000276:immunology / Q000473:pathology; D011237:Predictive Value of Tests; D016097:Simian Acquired Immunodeficiency Syndrome / Q000201:enzymology / Q000276:immunology* / Q000473:pathology*; D015302:Simian Immunodeficiency Virus / Q000276:immunology*; D019014:fas Receptor / Q000096:biosynthesis
chemical_list: D051033:Apoptosis Inducing Factor; D061945:Caspase Inhibitors; D019014:fas Receptor; D020169:Caspases