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
Citations
More filters
Journal ArticleDOI
Development of a DNA vaccine designed to induce cytotoxic T lymphocyte responses to multiple conserved epitopes in HIV-1.
Cara C. Wilson,Denise M. McKinney,Michelle Anders,Samantha MaWhinney,Jeri E. Forster,Claire Crimi,Scott Southwood,Alessandro Sette,Robert W. Chesnut,Mark Newman,Brian D. Livingston +10 more
TL;DR: Data indicate that the EP HIV-1090 DNA vaccine may be suitable for inducing relevant HIV-1-specific CTL responses in humans, similar to those induced by immunization with peptides.
Journal ArticleDOI
Plasmid Chemokines and Colony-Stimulating Factors Enhance the Immunogenicity of DNA Priming-Viral Vector Boosting Human Immunodeficiency Virus Type 1 Vaccines
Dan H. Barouch,Paul F. McKay,Shawn M. Sumida,Sampa Santra,Shawn S. Jackson,Darci A. Gorgone,Michelle A. Lifton,Bimal K. Chakrabarti,Ling Xu,Gary J. Nabel,Norman L. Letvin +10 more
TL;DR: It is demonstrated that plasmid cytokines can markedly improve the immunogenicity of DNA prime-viral vector boost vaccine strategies and can partially compensate for antivector immunity.
Journal ArticleDOI
T Cell Responses to Human Endogenous Retroviruses in HIV-1 Infection
Keith E. Garrison,R. Brad Jones,Duncan A. Meiklejohn,Naveed Anwar,Lishomwa C. Ndhlovu,Joan M. Chapman,Ann L Erickson,Ashish Agrawal,Gerald Spotts,Frederick Hecht,Seth Rakoff-Nahoum,Jack Lenz,Mario A. Ostrowski,Mario A. Ostrowski,Douglas F. Nixon +14 more
TL;DR: Data indicate that HIV-1 infection leads to HERV expression and stimulation of a HERV-specific CD8+ T cell response, which suggests that elicitation of anti-HERV- specific immune responses is a novel approach to immunotherapeutic vaccination.
Journal ArticleDOI
Vaccine Design for CD8 T Lymphocyte Responses
Richard A. Koup,Daniel C. Douek +1 more
TL;DR: The rationale behind a T-cell-based vaccine approach is reviewed, the methods and platforms that are being applied are provided, and the impact of recent vaccine trial results on the future direction of T- cell vaccine research is discussed.
Journal ArticleDOI
HIV-1 Epitope-Specific CD8+ T Cell Responses Strongly Associated with Delayed Disease Progression Cross-Recognize Epitope Variants Efficiently
Emma L. Turnbull,A R Lopes,Nicola A. Jones,David Cornforth,Phillipa Newton,D. Aldam,Pierre Pellegrino,Joanne Turner,I Williams,Craig M. Wilson,Paul A. Goepfert,Mala K. Maini,Persephone Borrow +12 more
TL;DR: It is shown that the epitope-specific responses exhibiting the most efficient cross-recognition of amino acid-substituted variants were those strongly associated with delayed progression to disease, consistent with the hypothesis that the reported associations between particular HLA class I alleles and rate of disease progression may be due to the quality of responses to certain “critical” epitopes.
References
More filters
Journal ArticleDOI
Molecular Beacons: Probes that Fluoresce upon Hybridization
Sanjay Tyagi,Fred Russell Kramer +1 more
TL;DR: Novel nucleic acid probes that recognize and report the presence of specific nucleic acids in homogeneous solutions that undergo a spontaneous conforma-tional change when they hybridize to their targets are developed.
Journal Article
Cell cycle analysis of a cell proliferation-associated human nuclear antigen defined by the monoclonal antibody Ki-67.
TL;DR: The data suggest that the early stages of mitogen stimulation represent initial sequences of proliferation and not parts of the cell cycle, and immunostaining with monoclonal antibody Ki-67 provides a reliable means of rapidly evaluating the growth fraction of normal and neoplastic human cell populations.
Journal ArticleDOI
HIV-1 Dynamics in Vivo: Virion Clearance Rate, Infected Cell Life-Span, and Viral Generation Time
TL;DR: A new mathematical model was used to analyze a detailed set of human immunodeficiency virus-type 1 (HIV-1) viral load data collected from five infected individuals after the administration of a potent inhibitor of HIV-1 protease, providing not only a kinetic picture ofAIDS pathogenesis, but also theoretical principles to guide the development of treatment strategies.
Journal ArticleDOI
Identification of RANTES, MIP-1α, and MIP-1β as the Major HIV-Suppressive Factors Produced by CD8+ T Cells
Fiorenza Cocchi,Anthony L. DeVico,Alfredo Garzino-Demo,Suresh K. Arya,Robert C. Gallo,Paolo Lusso +5 more
TL;DR: Recombinant human RANTES, Mip-1α, and MIP-1β induced a dose-dependent inhibition of different strains of HIV-1, HIV-2, and simian immunodeficiency virus (SIV) and may have relevance for the prevention and therapy of AIDS.
Journal ArticleDOI
Prognosis in HIV-1 Infection Predicted by the Quantity of Virus in Plasma
John W. Mellors,Charles R. Rinaldo,Phalguni Gupta,Roseanne M. White,John Todd,Lawrence A. Kingsley +5 more
TL;DR: Plasma viral load was a better predictor of progression to AIDS and death than was the number of CD4+ T cells, and the risk of acquired immunodeficiency syndrome (AIDS) and death in study subjects was directly related to plasma viral load at study entry.