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Title: Depletion of CD8+ cells does not affect the lifespan of productively infected cells during pathogenic sivmac239 infection of rhesus macaques

Abstract

While CD8+ T cell responses are clearly important in anti-viral immunity during HIV/SIV infection, the mechanisms by which CD8+ T cells induce this effect remain poorly understood, as emphasized by the failure of the Merck adenovirus-based, cytotoxic T lymphocyte (CTL)-inducing AIDS vaccine in a large phase IIb clinical trial. In this study, we measured the in vivo effect of CD8+ lymphocytes on the lifespan of productively infected cells during chronic SIVmac239 infection of rhesus macaques by treating two groups of animals (i.e., CD8+ lymphocyte-depleted or controls) with antiretroviral therapy (PMPA and FTC). The lifespan of productively infected cells was calculated based on the slope of the decline of SIV plasma viremia using a well-accepted mathematical model. We found that, in both early (i.e., day 57 post-inoculation) and late (i.e., day 177 post-inoculation) chronic SIV infection, depletion of CD8+ lymphocytes did not result in an increased lifespan of productively infected cells in vivo. This result indicates that direct killing of cells producing virus is unlikely to be a major mechanism underlying the anti-viral effect of CD8+ T cells during SIV infection. These results have profound implications for the development of AIDS vaccines.

Authors:
 [1];  [1];  [1]
  1. Los Alamos National Laboratory
Publication Date:
Research Org.:
Los Alamos National Laboratory (LANL), Los Alamos, NM (United States)
Sponsoring Org.:
USDOE
OSTI Identifier:
960599
Report Number(s):
LA-UR-08-05446; LA-UR-08-5446
TRN: US201006%%1240
DOE Contract Number:  
AC52-06NA25396
Resource Type:
Journal Article
Journal Name:
Nature Medicine
Additional Journal Information:
Journal Name: Nature Medicine
Country of Publication:
United States
Language:
English
Subject:
55; AIDS; AIDS VIRUS; ANIMALS; CLINICAL TRIALS; FAILURES; IMMUNITY; IN VIVO; LYMPHOCYTES; MACACUS; MATHEMATICAL MODELS; PLASMA; SIMIAN VIRUS; THERAPY; VACCINES

Citation Formats

Shudo, Emi, Ribeiro, Ruy M, and Perelson, Alan S. Depletion of CD8+ cells does not affect the lifespan of productively infected cells during pathogenic sivmac239 infection of rhesus macaques. United States: N. p., 2008. Web.
Shudo, Emi, Ribeiro, Ruy M, & Perelson, Alan S. Depletion of CD8+ cells does not affect the lifespan of productively infected cells during pathogenic sivmac239 infection of rhesus macaques. United States.
Shudo, Emi, Ribeiro, Ruy M, and Perelson, Alan S. 2008. "Depletion of CD8+ cells does not affect the lifespan of productively infected cells during pathogenic sivmac239 infection of rhesus macaques". United States. https://www.osti.gov/servlets/purl/960599.
@article{osti_960599,
title = {Depletion of CD8+ cells does not affect the lifespan of productively infected cells during pathogenic sivmac239 infection of rhesus macaques},
author = {Shudo, Emi and Ribeiro, Ruy M and Perelson, Alan S},
abstractNote = {While CD8+ T cell responses are clearly important in anti-viral immunity during HIV/SIV infection, the mechanisms by which CD8+ T cells induce this effect remain poorly understood, as emphasized by the failure of the Merck adenovirus-based, cytotoxic T lymphocyte (CTL)-inducing AIDS vaccine in a large phase IIb clinical trial. In this study, we measured the in vivo effect of CD8+ lymphocytes on the lifespan of productively infected cells during chronic SIVmac239 infection of rhesus macaques by treating two groups of animals (i.e., CD8+ lymphocyte-depleted or controls) with antiretroviral therapy (PMPA and FTC). The lifespan of productively infected cells was calculated based on the slope of the decline of SIV plasma viremia using a well-accepted mathematical model. We found that, in both early (i.e., day 57 post-inoculation) and late (i.e., day 177 post-inoculation) chronic SIV infection, depletion of CD8+ lymphocytes did not result in an increased lifespan of productively infected cells in vivo. This result indicates that direct killing of cells producing virus is unlikely to be a major mechanism underlying the anti-viral effect of CD8+ T cells during SIV infection. These results have profound implications for the development of AIDS vaccines.},
doi = {},
url = {https://www.osti.gov/biblio/960599}, journal = {Nature Medicine},
number = ,
volume = ,
place = {United States},
year = {Tue Jan 01 00:00:00 EST 2008},
month = {Tue Jan 01 00:00:00 EST 2008}
}