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Open AccessJournal ArticleDOI

Dramatic rise in plasma viremia after CD8+ T cell depletion in simian immunodeficiency virus-infected macaques

TLDR
It is demonstrated that CD8 cells play a crucial role in suppressing SIV replication in vivo and are examined using an anti-CD8 monoclonal antibody, OKT8F.
Abstract
To determine the role of CD8(+) T cells in controlling simian immunodeficiency virus (SIV) replication in vivo, we examined the effect of depleting this cell population using an anti-CD8 monoclonal antibody, OKT8F. There was on average a 99.9% reduction of CD8 cells in peripheral blood in six infected Macaca mulatta treated with OKT8F. The apparent CD8 depletion started 1 h after antibody administration, and low CD8 levels were maintained until day 8. An increase in plasma viremia of one to three orders of magnitude was observed in five of the six macaques. The injection of a control antibody to an infected macaque did not induce a sustained viral load increase, nor did it significantly reduce the number of CD8(+) T cells. These results demonstrate that CD8 cells play a crucial role in suppressing SIV replication in vivo.

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Accelerating HIV vaccine development using non-human primate models.

TL;DR: Use of NHP models has opened new research areas with outstanding potential for generating vaccine efficacy against HIV and other infectious agents and their utility and value in assessing immunogenicity and efficacy of novel vaccines have become apparent.
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Reduction of CD4+ T cells in vivo does not affect virus load in macaque elite controllers

TL;DR: Viral loads remained stable throughout the experiment, suggesting that SIV-specific CD4+ T cell responses may not play a direct role in controlling chronic viral replication in these elite controllers.
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Evidence for Gag p24-specific CD4 T cells with reduced susceptibility to R5 HIV-1 infection in a UK cohort of HIV-exposed-seronegative subjects.

TL;DR: SpecificCD4 cell immunity, characterized by a broadly directed memory Gag-p24 CD4 cell response and reduced susceptibility of specific CD4 cells to R5 HIV-1 infection, is a likely correlate of non-transmission.
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Model with Two Types of CTL regulation and Experiments on CTL Dynamics

TL;DR: The model is upgraded to take into account recent reports on the link between the activation status of infected cells and their ability to produce virus, the effect of helper cells at the time of priming on CTL differentiation, and virus dynamics in unvaccinated macaques with a broad genetic background acutely infected with SIVmac251.
References
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Journal ArticleDOI

Molecular Beacons: Probes that Fluoresce upon Hybridization

TL;DR: Novel nucleic acid probes that recognize and report the presence of specific nucleic acids in homogeneous solutions that undergo a spontaneous conforma-tional change when they hybridize to their targets are developed.
Journal Article

Cell cycle analysis of a cell proliferation-associated human nuclear antigen defined by the monoclonal antibody Ki-67.

TL;DR: The data suggest that the early stages of mitogen stimulation represent initial sequences of proliferation and not parts of the cell cycle, and immunostaining with monoclonal antibody Ki-67 provides a reliable means of rapidly evaluating the growth fraction of normal and neoplastic human cell populations.
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HIV-1 Dynamics in Vivo: Virion Clearance Rate, Infected Cell Life-Span, and Viral Generation Time

TL;DR: A new mathematical model was used to analyze a detailed set of human immunodeficiency virus-type 1 (HIV-1) viral load data collected from five infected individuals after the administration of a potent inhibitor of HIV-1 protease, providing not only a kinetic picture ofAIDS pathogenesis, but also theoretical principles to guide the development of treatment strategies.
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Identification of RANTES, MIP-1α, and MIP-1β as the Major HIV-Suppressive Factors Produced by CD8+ T Cells

TL;DR: Recombinant human RANTES, Mip-1α, and MIP-1β induced a dose-dependent inhibition of different strains of HIV-1, HIV-2, and simian immunodeficiency virus (SIV) and may have relevance for the prevention and therapy of AIDS.
Journal ArticleDOI

Prognosis in HIV-1 Infection Predicted by the Quantity of Virus in Plasma

TL;DR: Plasma viral load was a better predictor of progression to AIDS and death than was the number of CD4+ T cells, and the risk of acquired immunodeficiency syndrome (AIDS) and death in study subjects was directly related to plasma viral load at study entry.
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