title: Changes in soluble factor-mediated CD8+ cell-derived antiviral activity in cynomolgus macaques infected with simian immunodeficiency virus SIVmac251: relationship to biological markers of progression.
abstract: Cross-sectional studies have shown that the capacity of CD8+ cells from human immunodeficiency virus (HIV)-infected patients and simian immunodeficiency virus (SIV) SIVmac-infected macaques to suppress the replication of human and simian immunodeficiency viruses in vitro depends on the clinical stage of disease, but little is known about changes in this antiviral activity over time in individual HIV-infected patients or SIV-infected macaques. We assessed changes in the soluble factor-mediated noncytolytic antiviral activity of CD8+ cells over time in eight cynomolgus macaques infected with SIVmac251 to determine the pathophysiological role of this activity. CD8+ cell-associated antiviral activity increased rapidly in the first week after viral inoculation and remained detectable during the early phase of infection. The net increase in antiviral activity of CD8+ cells was correlated with plasma viral load throughout the 15 months of follow-up. CD8+ cells gradually lost their antiviral activity over time and acquired virus replication-enhancing capacity. Levels of antiviral activity correlated with CD4+ T-cell counts after viral set point. Concentrations of beta-chemokines and interleukin-16 in CD8+ cell supernatants were not correlated with this antiviral activity, and alpha-defensins were not detected. The soluble factor-mediated antiviral activity of CD8+ cells was neither cytolytic nor restricted to major histocompatibility complex. This longitudinal study strongly suggests that the increase in noncytolytic antiviral activity from baseline and the maintenance of this increase over time in cynomolgus macaques depend on both viral replication and CD4+ T cells.
authors.affiliation: CEA, Laboratoire d'Immunopathologie Expérimentale, Service de Neurovirologie, DSV/DRM, EPHE, IPSC, Université Paris XI UMRE01, 18, Route du Panorama, BP 6, 92 265 Fontenay aux Roses, France.
authors.forename: Vincent
authors.initials: V
authors.lastname: Dioszeghy
authors.forename: Kadija
authors.initials: K
authors.lastname: Benlhassan-Chahour
authors.forename: Benoit
authors.initials: B
authors.lastname: Delache
authors.forename: Nathalie
authors.initials: N
authors.lastname: Dereuddre-Bosquet
authors.forename: Celine
authors.initials: C
authors.lastname: Aubenque
authors.forename: Gabriel
authors.initials: G
authors.lastname: Gras
authors.forename: Roger
authors.initials: R
authors.lastname: Le Grand
authors.forename: Bruno
authors.initials: B
authors.lastname: Vaslin
mesh_terms: D000818:Animals; D015415:Biomarkers; D018414:CD8-Positive T-Lymphocytes / Q000737:chemistry* / Q000276:immunology; D018450:Disease Progression; D008137:Longitudinal Studies; D008253:Macaca mulatta; D016097:Simian Acquired Immunodeficiency Syndrome / Q000276:immunology* / Q000473:pathology; D015302:Simian Immunodeficiency Virus / Q000276:immunology* / Q000502:physiology
chemical_list: D015415:Biomarkers