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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Development of a DNA-MVA/HIVA vaccine for Kenya.
Tomáš Hanke,Andrew J. McMichael,Matilu Mwau,Edmund G.-T. Wee,Inese Ceberej,Sandip Patel,Julian Sutton,Maxine Tomlinson,Rachel V. Samuel +8 more
TL;DR: In this article, the authors proposed a prime-boost immunogen, termed HIVA, to match the HIV strain responsible locally for over 70% infections in the Kenyan population, which consists of a consensus clade A (clade p24/p17) and a string of CLade A-derived CTL epitopes.
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Targeting of a CD8 T cell env epitope presented by HLA-B*5802 is associated with markers of HIV disease progression and lack of selection pressure.
Kholiswa C. Ngumbela,Cheryl L. Day,Zenele Mncube,Kriebashnie Nair,Dhanwanthie Ramduth,Christina F. Thobakgale,Eshia Moodley,Sharon Reddy,C. de Pierres,Nompumelelo Mkhwanazi,Karen S. Bishop,M van der Stok,Nasreen Ismail,Isobella Honeyborne,Hayley Crawford,Daniel G. Kavanagh,Christine Rousseau,David C. Nickle,James I. Mullins,David Heckerman,Bette T. Korber,Hoosen M. Coovadia,Photini Kiepiela,Philip J. R. Goulder,Bruce D. Walker +24 more
TL;DR: Experimental evidence is provided that not all epitope-specific responses contribute to immune containment, and that selective targeting of Env through HLA-B*5802 is at least ineffectual if not actively adverse in the containment of viremia.
Journal ArticleDOI
Frequency and function of HIV-specific CD8(+) T cells.
Stephen A. Migueles,Mark Connors +1 more
TL;DR: The data demonstrate that high numbers of HIV-specific CD8(+) T cells exist even in patients with high level viremia and progressive disease and suggest that other qualitative parameters of the CD8 (+) T cell response may differentiate some patients with very low levels of plasma virus and nonprogressive infection.
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Activated CD4+CCR5+ T cells in the rectum predict increased SIV acquisition in SIVGag/Tat-vaccinated rhesus macaques.
Diane G. Carnathan,Katherine S. Wetzel,Joana Yu,S. Thera Lee,Brent A. Johnson,Mirko Paiardini,Jian Yan,Matthew P. Morrow,Niranjan Y. Sardesai,David B. Weiner,Hildegund C.J. Ertl,Guido Silvestri +11 more
TL;DR: This study showed that the presence of higher levels of activated CD4+ T cells in mucosal tissues is associated with increased risk of breakthrough SIV infection in vaccinated animals, and evaluated five immunization strategies that include Human adenovirus-5 (AdHu5), Chimpanzee adenOVirus-6 (AdC6) or -7, Vaccinia virus (VV), and DNA given by electroporation (DNA/EP).
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The Antiviral Efficacy of Simian Immunodeficiency Virus-Specific CD8+ T Cells Is Unrelated to Epitope Specificity and Is Abrogated by Viral Escape
John T. Loffredo,Benjamin J. Burwitz,Eva G. Rakasz,Sean P. Spencer,Jason J. Stephany,Juan Pablo Giraldo Vela,Sarah Martin,Jason S. Reed,Shari M. Piaskowski,Jessica Furlott,Kim L. Weisgrau,Denise S. Rodrigues,Taeko Soma,Gnankang Napoé,Thomas C. Friedrich,Nancy A. Wilson,Esper G. Kallas,David I. Watkins +17 more
TL;DR: Viral escape abrogated the abilities of Tat28-35SL8- and Gag181-189CM9-specific CD8+ T cells to control viral replication, but gamma interferon enzyme-linked immunospot and IFN-γ/tumor necrosis factor alpha intracellular-cytokine-staining assays detected cross-reactive immune responses against the Gag escape variant.
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