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

Journal Article · Tue Jan 01 04:00:00 EST 2008 · Nature Medicine

OSTI ID:960599

Shudo, Emi ^[1]; Ribeiro, Ruy M ^[1]; Perelson, Alan S ^[1]

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1. Los Alamos National Laboratory

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.

• Research Organization: Los Alamos National Laboratory (LANL)
• Sponsoring Organization: DOE
• DOE Contract Number: AC52-06NA25396
• OSTI ID: 960599
• Report Number(s): LA-UR-08-05446; LA-UR-08-5446
• Journal Information: Nature Medicine, Journal Name: Nature Medicine
• Country of Publication: United States
• Language: English

Related Subjects

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AIDS
AIDS VIRUS
ANIMALS
CLINICAL TRIALS
FAILURES
IMMUNITY
IN VIVO
LYMPHOCYTES
MACACUS
MATHEMATICAL MODELS
PLASMA
SIMIAN VIRUS
THERAPY
VACCINES