Effects of in Vivo Cd8+ T Cell Depletion on Virus Replication in Rhesus Macaques Immunized with a Live, Attenuated Simian Immunodeficiency Virus Vaccine

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.

doi:10.1084/jem.191.11.1921

Title: Effects of in Vivo Cd8⁺ T Cell Depletion on Virus Replication in Rhesus Macaques Immunized with a Live, Attenuated Simian Immunodeficiency Virus Vaccine

Journal Article · Sun Jun 06 00:00:00 EDT 1999 · Journal of Experimental Medicine

DOI:https://doi.org/10.1084/jem.191.11.1921· OSTI ID:1625182

Metzner, Karin J. ^[1]; Jin, Xia ^[1]; Lee, Fred V. ^[1]; Gettie, Agegnehu ^[1]; Bauer, Daniel E. ^[1]; Di Mascio, Michele ^[2]; Perelson, Alan S. ^[2]; Marx, Preston A. ^[3]; Ho, David D. ^[1]; Kostrikis, Leondios G. ^[1]; Connor, Ruth I. ^[1]

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)

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.

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Research Organization:: Los Alamos National Laboratory (LANL), Los Alamos, NM (United States)

Sponsoring Organization:: 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

Grant/Contract Number:: AC52-06NA25396; RR06555; AI43868

OSTI ID:: 1625182

Journal Information:: Journal of Experimental Medicine, Vol. 191, Issue 11; ISSN 0022-1007

Publisher:: Rockefeller University PressCopyright Statement

Country of Publication:: United States

Language:: English

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59 BASIC BIOLOGICAL SCIENCES
simian immunodeficiency virus
live attenuated vaccine
OKT8F
CD8+ T lymphocytes
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Title: Effects of in Vivo Cd8+ T Cell Depletion on Virus Replication in Rhesus Macaques Immunized with a Live, Attenuated Simian Immunodeficiency Virus Vaccine

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Title: Effects of in Vivo Cd8⁺ T Cell Depletion on Virus Replication in Rhesus Macaques Immunized with a Live, Attenuated Simian Immunodeficiency Virus Vaccine