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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T cell responses to viral infections: lessons from lymphocytic choriomeningitis virus.
TL;DR: Some of the findings using LCMV infection of mice as well as their relevance to other infections of animals and humans are discussed.
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T cell exhaustion and immune-mediated disease-the potential for therapeutic exhaustion.
TL;DR: Modulation of T cell exhaustion can restore function in exhausted CD8 T cells, promoting viral clearance and facilitate novel treatment approaches for autoimmunity through the therapeutic induction of exhaustion.
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Cooperation of TNF Family Members CD40 Ligand, Receptor Activator of NF-κB Ligand, and TNF-α in the Activation of Dendritic Cells and the Expansion of Viral Specific CD8+ T Cell Memory Responses in HIV-1-Infected and HIV-1-Uninfected Individuals
TL;DR: It is demonstrated that optimal maturation of DCs requires multiple signals by TNF superfamily members that include CD40L, and in HIV-1 infection, DCs may only requireCD40L to maximally expand CTL, suggesting that CD4+ T cells can provide help to CD8- T cells independently of CD40 L, RANKL, or TNF-α.
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Small variations in multiple parameters account for wide variations in HIV-1 set-points: a novel modelling approach.
TL;DR: A novel model is developed by providing explicit expressions for the process functions having the highest patient–to–patient variation in their estimated values, which accounted for the large variations observed in the steady–state viral burden of HIV–1 infections.
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Nef interference with HIV-1-specific CTL antiviral activity is epitope specific.
Sama Adnan,Arumugam Balamurugan,Arumugam Balamurugan,Alicja Trocha,Alicja Trocha,Michael S. Bennett,Michael S. Bennett,Hwee L. Ng,Hwee L. Ng,Ayub Ali,Ayub Ali,Christian Brander,Christian Brander,Otto O. Yang,Otto O. Yang +14 more
TL;DR: Examination of the impact of Nef on the antiviral activity of several CTL clones recognizing epitopes from early and late HIV-1 proteins suggests that HLA-C-restricted CTLs may have an under-appreciated antiviral role in the setting of Nf in vivo and suggest a benefit of promoting HLA -C- restricted CTLS for immunotherapy or vaccine development.
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