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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SIV-specific CD8+ T cells express high levels of PD1 and cytokines but have impaired proliferative capacity in acute and chronic SIVmac251 infection
Constantinos Petrovas,David Price,David Price,Joseph J. Mattapallil,David R. Ambrozak,Christof Geldmacher,Valentina Cecchinato,Monica Vaccari,Elzbieta Tryniszewska,Emma Gostick,Mario Roederer,Daniel C. Douek,Sara H. Morgan,Simon J. Davis,Genoveffa Franchini,Richard A. Koup +15 more
TL;DR: PD-1 is a negative regulator of SIV-specific CD8+ T cells, operating predominantly through the induction of cell death, and Manipulation of the interaction of PD-1 with its ligands could thus potentially restore the CD8- T-cell responses in SIV infection.
Journal ArticleDOI
Transfer of specificity for human immunodeficiency virus type 1 into primary human T lymphocytes by introduction of T-cell receptor genes.
Laurence J.N. Cooper,Michael Kalos,Deborah A. Lewinsohn,Stanley R. Riddell,Stanley R. Riddell,Philip D. Greenberg,Philip D. Greenberg +6 more
TL;DR: The results demonstrate that the high level of TCR expression required for physiologic functioning can be reproducibly achieved with retroviral vectors encoding full-length unmodified TCR chains under the control of a strong internal constitutive phosphoglycerate kinase promoter.
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CD8+ T cell differentiation and dysfunction in cancer
Mary Philip,Andrea Schietinger +1 more
TL;DR: In this paper, a review of CD8+ T cell differentiation to dysfunctional states during tumorigenesis is presented, highlighting similarities and differences between T cell dysfunction and other hyporesponsive T cell states and discuss the spatio-temporal factors contributing to T cell state heterogeneity in tumours.
Journal ArticleDOI
Adenovirus vector-based vaccines for human immunodeficiency virus type 1.
Dan H. Barouch,Gary J. Nabel +1 more
TL;DR: Progress is described in the development of rAd vector-based vaccines with a focus on human immunodeficiency virus type 1, and the inherent immunogenicity of these vectors is a desirable feature for vaccine development.
Journal ArticleDOI
Innate immune recognition and activation during HIV infection
TL;DR: Current knowledge on innate immune recognition and activation during HIV infection is presented based on studies in cell culture, non-human primates, and HIV-infected individuals, and the implications for the understanding of HIV immunopathogenesis are discussed.
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