Dramatic rise in plasma viremia after CD8+ T cell depletion in simian immunodeficiency virus-infected macaques
Xia Jin,Daniel E. Bauer,Sarah Tuttleton,Sharon R Lewin,Agegnehu Gettie,James Blanchard,Craig E. Irwin,Jeffrey T. Safrit,John E. Mittler,Leor S. Weinberger,Leondios G. Kostrikis,Linqi Zhang,Alan S. Perelson,David D. Ho +13 more
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.read more
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Human immunodeficiency virus-specific gamma interferon enzyme-linked immunospot assay responses targeting specific regions of the proteome during primary subtype C infection are poor predictors of the course of viremia and set point.
Clive M. Gray,Mandla Mlotshwa,Catherine Riou,Tiyani Mathebula,Debra de Assis Rosa,Tumelo Mashishi,Cathal Seoighe,Nobubelo Ngandu,Francois van Loggerenberg,Lynn Morris,Koleka Mlisana,Carolyn Williamson,Salim S. Abdool Karim +12 more
TL;DR: The magnitude and breadth of IFN-γ ELISPOT assay responses at 3 months postinfection are unrelated to the course of disease in the first year of infection and are not associated with, and have low predictive power for, the viral set point at 12 months.
Journal ArticleDOI
CD8+ T‐cell effector function and transcriptional regulation during HIV pathogenesis
TL;DR: The evidence for CD8+ T cells as correlates of protection, the means by which their antiviral capacity is evaluated, and transcription factors responsible for their function, or dysfunction, during HIV infection are discussed.
Journal ArticleDOI
Depletion of CD8 + Cells in Sooty Mangabey Monkeys Naturally Infected with Simian Immunodeficiency Virus Reveals Limited Role for Immune Control of Virus Replication in a Natural Host Species
Ashley P. Barry,Guido Silvestri,Guido Silvestri,Jeffrey T. Safrit,Beth Sumpter,Natalia Kozyr,Harold M. McClure,Silvija I. Staprans,Mark B. Feinberg +8 more
TL;DR: Data indicate that CD8+ T cells exert a limited influence in determining the levels of SIV replication in SMs and provide additional evidence demonstrating that the absence of AIDS in SIV-infected SMs is not due to the effective control of viral replication by cellular immune responses.
Journal ArticleDOI
Enhanced cellular immunity and systemic control of SHIV infection by combined parenteral and mucosal administration of a DNA prime MVA boost vaccine regimen
Barbro Mäkitalo,Barbro Mäkitalo,Peter Lundholm,Jorma Hinkula,Charlotta Nilsson,Charlotta Nilsson,K. Karlén,Andreas Mörner,Gerd Sutter,Volker Erfle,Jonathan L. Heeney,Britta Wahren,Britta Wahren,Gunnel Biberfeld,Gunnel Biberfeld,Rigmor Thorstensson +15 more
TL;DR: Strong cellular immune responses and reduction of challenge virus burden were demonstrated in animals immunized i.m. and i.r.o. only following homologous intravenous simian-human immunodeficiency virus (SHIV) challenge, and the breadth and magnitude of the induced immune responses correlated with protective efficacy.
Journal ArticleDOI
Understanding the failure of CD8 T-cell vaccination against simian/human immunodeficiency virus
TL;DR: Novel mathematical models are parameterized for acute SIV and human immunodeficiency virus infection to explain that failure of vaccination is due to the fact that effector/target ratios are too low during the viral expansion phase.
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