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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Preservation of T Cell Proliferation Restricted by Protective HLA Alleles Is Critical for Immune Control of HIV-1 Infection
Helen Horton,Ian Frank,Ruth Baydo,Emilie Jalbert,Justin Penn,Sean Wilson,John McNevin,Matthew D. McSweyn,Deborah Lee,Yunda Huang,Stephen C. De Rosa,M. Juliana McElrath +11 more
TL;DR: The capacity to maintain CD8+ T cell proliferation, regardless of MHC-restriction, may serve as an important correlate of disease protection in the event of infection following vaccination.
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Phenotypic and Functional Profile of HIV-Inhibitory CD8 T Cells Elicited by Natural Infection and Heterologous Prime/Boost Vaccination
Stephanie A. Freel,Laurie Lamoreaux,Pratip K. Chattopadhyay,Kevin O. Saunders,David Zarkowsky,Overman Rg,Christina Ochsenbauer,Tara G. Edmonds,John C. Kappes,Coleen K. Cunningham,Thomas N. Denny,Kent J. Weinhold,Guido Ferrari,Barton F. Haynes,Richard A. Koup,Barney S. Graham,Mario Roederer,Georgia D. Tomaras +17 more
TL;DR: The authors showed that vaccination against HIV-1 Env and Gag-Pol by DNA priming followed by recombinant adenovirus type 5 (rAd5) boosting elicited CD8+ T-cell-mediated antiviral activity against several viruses with either lab-adapted or transmitted virus envelopes.
Journal ArticleDOI
Polyfunctional analysis of human t cell responses: importance in vaccine immunogenicity and natural infection.
TL;DR: The SIV/rhesus macaque experimental system has provided compelling evidence in support of a role for T cells in the control of HIV/SIV replication, and researchers have more recently focused on vaccine candidates that will primarily stimulate cellular immune responses against HIV.
Journal ArticleDOI
Effect of CD8+ Lymphocyte Depletion on Virus Containment after Simian Immunodeficiency Virus SIVmac251 Challenge of Live Attenuated SIVmac239Δ3-Vaccinated Rhesus Macaques
Jörn E. Schmitz,R. Paul Johnson,Harold M. McClure,Kelledy Manson,Michael S. Wyand,Marcelo J. Kuroda,Michelle A. Lifton,Rajinder Khunkhun,Kimberly J. McEvers,Jacqueline Gillis,Michael Piatak,Jeffrey D. Lifson,Gudrun Großschupff,Paul Racz,Klara Tenner-Racz,E. Peter Rieber,Kristine Kuus-Reichel,Rebecca Gelman,Norman L. Letvin,David C. Montefiori,Ruth M. Ruprecht,Ronald C. Desrosiers,Keith A. Reimann +22 more
TL;DR: The partial control of postchallenge viremia after CD8+ lymphocyte depletion suggests that both humoral and cellular immune responses induced by live attenuated SIV vaccines can contribute to protection against a pathogenic challenge and that the relative contribution of each of these responses to protection may be genetically determined.
Journal ArticleDOI
The function and dysfunction of memory CD8+ T cells in tumor immunity.
James L. Reading,Felipe Gálvez-Cancino,Charles Swanton,Alvaro Lladser,Karl S. Peggs,Sergio A. Quezada +5 more
TL;DR: The potential significance of circulating effector cells poised downstream of neoantigen recognition and upstream of T cell dysfunction are elucidated and it is proposed that cells in this immunological ‘sweet spot’ may be key anti‐tumor effectors.
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