Effects of in Vivo Cd8+ T Cell Depletion on Virus Replication in Rhesus Macaques Immunized with a Live, Attenuated Simian Immunodeficiency Virus Vaccine
Abstract
The role of CD8+ T lymphocytes in controlling replication of live, attenuated simian immunodeficiency virus (SIV) was investigated as part of a vaccine study to examine the correlates of protection in the SIV/rhesus macaque model. Rhesus macaques immunized for > 2 yr with nef-deleted SIV (SIVmac239Δnef) and protected from challenge with pathogenic SIVmac251 were treated with anti-CD8 antibody (OKT8F) to deplete CD8+ T cells in vivo. The effects of CD8 depletion on viral load were measured using a novel quantitative assay based on real-time polymerase chain reaction using molecular beacons. This assay allows simultaneous detection of both the vaccine strain and the challenge virus in the same sample, enabling direct quantification of changes in each viral population. Our results show that CD8+ T cells were depleted within 1 h after administration of OKT8F, and were reduced by as much as 99% in the peripheral blood. CD8+ T cell depletion was associated with a 1–2 log increase in SIVmac239Δnef plasma viremia. Control of SIVmac239Δnef replication was temporally associated with the recovery of CD8+ T cells between days 8 and 10. The challenge virus, SIVmac251, was not detectable in either the plasma or lymph nodes after depletion of CD8+ T cells. Overall,more »
- Authors:
-
- Rockefeller University, New York, NY (United States)
- Los Alamos National Laboratory (LANL), Los Alamos, NM (United States)
- Rockefeller University, New York, NY (United States); Tulane Regional Primate Research Center, Covington, LA (United States)
- Publication Date:
- Research Org.:
- Los Alamos National Laboratory (LANL), Los Alamos, NM (United States)
- Sponsoring Org.:
- USDOE Office of Science (SC), Biological and Environmental Research (BER). Biological Systems Science Division; National Institutes of Health (NIH); German Research Foundation (DFG); Irene Diamond Fund
- OSTI Identifier:
- 1625182
- Grant/Contract Number:
- AC52-06NA25396; RR06555; AI43868
- Resource Type:
- Accepted Manuscript
- Journal Name:
- Journal of Experimental Medicine
- Additional Journal Information:
- Journal Volume: 191; Journal Issue: 11; Journal ID: ISSN 0022-1007
- Publisher:
- Rockefeller University Press
- Country of Publication:
- United States
- Language:
- English
- Subject:
- 59 BASIC BIOLOGICAL SCIENCES; simian immunodeficiency virus; live attenuated vaccine; OKT8F; CD8+ T lymphocytes; differential PCR
Citation Formats
Metzner, Karin J., Jin, Xia, Lee, Fred V., Gettie, Agegnehu, Bauer, Daniel E., Di Mascio, Michele, Perelson, Alan S., Marx, Preston A., Ho, David D., Kostrikis, Leondios G., and Connor, Ruth I. Effects of in Vivo Cd8+ T Cell Depletion on Virus Replication in Rhesus Macaques Immunized with a Live, Attenuated Simian Immunodeficiency Virus Vaccine. United States: N. p., 1999.
Web. doi:10.1084/jem.191.11.1921.
Metzner, Karin J., Jin, Xia, Lee, Fred V., Gettie, Agegnehu, Bauer, Daniel E., Di Mascio, Michele, Perelson, Alan S., Marx, Preston A., Ho, David D., Kostrikis, Leondios G., & Connor, Ruth I. Effects of in Vivo Cd8+ T Cell Depletion on Virus Replication in Rhesus Macaques Immunized with a Live, Attenuated Simian Immunodeficiency Virus Vaccine. United States. https://doi.org/10.1084/jem.191.11.1921
Metzner, Karin J., Jin, Xia, Lee, Fred V., Gettie, Agegnehu, Bauer, Daniel E., Di Mascio, Michele, Perelson, Alan S., Marx, Preston A., Ho, David D., Kostrikis, Leondios G., and Connor, Ruth I. Sun .
"Effects of in Vivo Cd8+ T Cell Depletion on Virus Replication in Rhesus Macaques Immunized with a Live, Attenuated Simian Immunodeficiency Virus Vaccine". United States. https://doi.org/10.1084/jem.191.11.1921. https://www.osti.gov/servlets/purl/1625182.
@article{osti_1625182,
title = {Effects of in Vivo Cd8+ T Cell Depletion on Virus Replication in Rhesus Macaques Immunized with a Live, Attenuated Simian Immunodeficiency Virus Vaccine},
author = {Metzner, Karin J. and Jin, Xia and Lee, Fred V. and Gettie, Agegnehu and Bauer, Daniel E. and Di Mascio, Michele and Perelson, Alan S. and Marx, Preston A. and Ho, David D. and Kostrikis, Leondios G. and Connor, Ruth I.},
abstractNote = {The role of CD8+ T lymphocytes in controlling replication of live, attenuated simian immunodeficiency virus (SIV) was investigated as part of a vaccine study to examine the correlates of protection in the SIV/rhesus macaque model. Rhesus macaques immunized for > 2 yr with nef-deleted SIV (SIVmac239Δnef) and protected from challenge with pathogenic SIVmac251 were treated with anti-CD8 antibody (OKT8F) to deplete CD8+ T cells in vivo. The effects of CD8 depletion on viral load were measured using a novel quantitative assay based on real-time polymerase chain reaction using molecular beacons. This assay allows simultaneous detection of both the vaccine strain and the challenge virus in the same sample, enabling direct quantification of changes in each viral population. Our results show that CD8+ T cells were depleted within 1 h after administration of OKT8F, and were reduced by as much as 99% in the peripheral blood. CD8+ T cell depletion was associated with a 1–2 log increase in SIVmac239Δnef plasma viremia. Control of SIVmac239Δnef replication was temporally associated with the recovery of CD8+ T cells between days 8 and 10. The challenge virus, SIVmac251, was not detectable in either the plasma or lymph nodes after depletion of CD8+ T cells. Overall, our results indicate that CD8+ T cells play an important role in controlling replication of live, attenuated SIV in vivo.},
doi = {10.1084/jem.191.11.1921},
journal = {Journal of Experimental Medicine},
number = 11,
volume = 191,
place = {United States},
year = {Sun Jun 06 00:00:00 EDT 1999},
month = {Sun Jun 06 00:00:00 EDT 1999}
}
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