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Title: Dramatic Rise in Plasma Viremia after CD8+ T Cell Depletion in Simian Immunodeficiency Virus–infected Macaques

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.

Authors:
 [1];  [1];  [1];  [1];  [1];  [2];  [1];  [3];  [4];  [4];  [1];  [1];  [4];  [1]
  1. Rockefeller University, New York, NY (United States)
  2. Tulane Regional Primate Research Center, Covington, LA (United States)
  3. Emory University, Atlanta, GA (United States)
  4. Los Alamos National Laboratory (LANL), Los Alamos, NM (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); Bristol Myers Squibb Foundation; Irene Diamond Fund
OSTI Identifier:
1625181
Grant/Contract Number:  
AC52-06NA25396; AI40387; AI42848; AI43042; AI38573
Resource Type:
Accepted Manuscript
Journal Name:
Journal of Experimental Medicine
Additional Journal Information:
Journal Volume: 189; Journal Issue: 6; Journal ID: ISSN 0022-1007
Publisher:
Rockefeller University Press
Country of Publication:
United States
Language:
English
Subject:
59 BASIC BIOLOGICAL SCIENCES; immunology; research and experimental medicine; simian immunodeficiency virus; macaque; OKT8; viremia; cytotoxic T lymphocyte

Citation Formats

Jin, Xia, Bauer, Daniel E., Tuttleton, Sarah E., Lewin, Sharon, Gettie, Agegnehu, Blanchard, James, Irwin, Craig E., Safrit, Jeffrey T., Mittler, John, Weinberger, Leor, Kostrikis, Leondios G., Zhang, Linqi, Perelson, Alan S., and Ho, David D. Dramatic Rise in Plasma Viremia after CD8+ T Cell Depletion in Simian Immunodeficiency Virus–infected Macaques. United States: N. p., 1999. Web. doi:10.1084/jem.189.6.991.
Jin, Xia, Bauer, Daniel E., Tuttleton, Sarah E., Lewin, Sharon, Gettie, Agegnehu, Blanchard, James, Irwin, Craig E., Safrit, Jeffrey T., Mittler, John, Weinberger, Leor, Kostrikis, Leondios G., Zhang, Linqi, Perelson, Alan S., & Ho, David D. Dramatic Rise in Plasma Viremia after CD8+ T Cell Depletion in Simian Immunodeficiency Virus–infected Macaques. United States. https://doi.org/10.1084/jem.189.6.991
Jin, Xia, Bauer, Daniel E., Tuttleton, Sarah E., Lewin, Sharon, Gettie, Agegnehu, Blanchard, James, Irwin, Craig E., Safrit, Jeffrey T., Mittler, John, Weinberger, Leor, Kostrikis, Leondios G., Zhang, Linqi, Perelson, Alan S., and Ho, David D. Mon . "Dramatic Rise in Plasma Viremia after CD8+ T Cell Depletion in Simian Immunodeficiency Virus–infected Macaques". United States. https://doi.org/10.1084/jem.189.6.991. https://www.osti.gov/servlets/purl/1625181.
@article{osti_1625181,
title = {Dramatic Rise in Plasma Viremia after CD8+ T Cell Depletion in Simian Immunodeficiency Virus–infected Macaques},
author = {Jin, Xia and Bauer, Daniel E. and Tuttleton, Sarah E. and Lewin, Sharon and Gettie, Agegnehu and Blanchard, James and Irwin, Craig E. and Safrit, Jeffrey T. and Mittler, John and Weinberger, Leor and Kostrikis, Leondios G. and Zhang, Linqi and Perelson, Alan S. and Ho, David D.},
abstractNote = {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.},
doi = {10.1084/jem.189.6.991},
journal = {Journal of Experimental Medicine},
number = 6,
volume = 189,
place = {United States},
year = {Mon Mar 15 00:00:00 EST 1999},
month = {Mon Mar 15 00:00:00 EST 1999}
}

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