Effects of In Vivo CD8+ T Cell Depletion on Virus Replication in Rhesus Macaques Immunized with a Live, Attenuated Simian Immunodeficiency Virus Vaccine

doi:10.1084/jem.191.11.1921

Published online 6 June 1999.

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© The Rockefeller University Press, 0022-1007/2000/6/1921/ $5.00
The Journal of Experimental Medicine, Volume 191, Number 11, June 5, 2000 1921-1932

Original Article

Effects of In Vivo CD8⁺ T Cell Depletion on Virus Replication in Rhesus Macaques Immunized with a Live, Attenuated Simian Immunodeficiency Virus Vaccine

Karin J. Metzner^a, Xia Jin^a, Fred V. Lee^a, Agegnehu Gettie^a, Daniel E. Bauer^a, Michele Di Mascio^b, Alan S. Perelson^b, Preston A. Marx^a,c, David D. Ho^a, Leondios G. Kostrikis^a, and Ruth I. Connor^a
^a Aaron Diamond AIDS Research Center, The Rockefeller University, New York, NewYork 10016
^b Theoretical Division, Los Alamos National Laboratory, Los Alamos, New Mexico 87545
^c Tulane Regional Primate Research Center, Covington, Louisiana 70433

Correspondence to: Ruth I. Connor, Aaron Diamond AIDS Research Center, 455 First Ave., 7th Fl., New York, NY 10016. Tel:212-448-5040 Fax:212-725-1126 E-mail:rconnor{at}adarc.org.

The role of CD8⁺ T lymphocytes in controlling replication oflive, attenuated simian immunodeficiency virus (SIV) was investigatedas part of a vaccine study to examine the correlates of protectionin the SIV/rhesus macaque model. Rhesus macaques immunized for>2 yr with nef-deleted SIV (SIVmac239 ${Delta}$ nef) and protected fromchallenge with pathogenic SIVmac251 were treated with anti-CD8antibody (OKT8F) to deplete CD8⁺ T cells in vivo. The effectsof CD8 depletion on viral load were measured using a novel quantitativeassay based on real-time polymerase chain reaction using molecularbeacons. This assay allows simultaneous detection of both thevaccine strain and the challenge virus in the same sample, enablingdirect quantification of changes in each viral population. Ourresults show that CD8⁺ T cells were depleted within 1 h afteradministration of OKT8F, and were reduced by as much as 99%in the peripheral blood. CD8⁺ T cell depletion was associatedwith a 1–2 log increase in SIVmac239 ${Delta}$ nef plasma viremia.Control of SIVmac239 ${Delta}$ nef replication was temporally associatedwith the recovery of CD8⁺ T cells between days 8 and 10. Thechallenge virus, SIVmac251, was not detectable in either theplasma or lymph nodes after depletion of CD8⁺ T cells. Overall,our results indicate that CD8⁺ T cells play an important rolein controlling replication of live, attenuated SIV in vivo.

Key Words: simian immunodeficiency virus, live attenuated vaccine, OKT8F,CD8⁺ T lymphocytes, differential PCR

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