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J Gen Virol 86 (2005), 3375-3384; DOI 10.1099/vir.0.81206-0

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© 2005 Society for General Microbiology

Evaluation of CD8+ T-cell and antibody responses following transient increased viraemia in rhesus macaques infected with live, attenuated simian immunodeficiency virus

Karin J. Metzner1,{dagger}, Walter J. Moretto2, Sean M. Donahoe1,{ddagger}, Xia Jin3, Agegnehu Gettie1, David C. Montefiori4, Preston A. Marx5, James M. Binley6, Douglas F. Nixon2 and Ruth I. Connor1,§

1 Aaron Diamond AIDS Research Center and The Rockefeller University, New York, NY 10016, USA
2 Gladstone Institute of Virology and Immunology, University of California, San Francisco, CA 94103, USA
3 University of Rochester Medicine Center, 601 Elmwood Avenue, Box 689, Rochester, NY 14642, USA
4 Center for AIDS Research, Department of Surgery, Duke University Medical Center, Durham, NC 27710, USA
5 Tulane Regional Primate Research Center and Department of Tropical Medicine, Tulane University Health Sciences Center, Covington, LA 70433, USA
6 Torrey Pines Institute for Molecular Studies, 3550 General Atomics Court, San Diego, CA 92121, USA

Correspondence
Ruth I. Connor
Ruth.Connor{at}Dartmouth.edu

In vivo depletion of CD8+ T cells results in an increase in viral load in macaques chronically infected with simian immunodeficiency virus (SIVmac239{Delta}nef). Here, the cellular and humoral immune responses associated with this transient period of enhanced viraemia in macaques infected with SIVmac239{Delta}nef were characterized. Fourteen days after in vivo CD8+ T-cell depletion, two of six macaques experienced a 1–2 log10 increase in anti-gp130 and p27 antibody titres and a three- to fivefold increase in gamma interferon-secreting SIV-specific CD8+ T cells. Three other macaques had modest or no increase in anti-gp130 antibodies and significantly lower titres of anti-p27 antibodies, with minimal induction of functional CD8+ T cells. Four of the five CD8-depleted macaques experienced an increase in neutralizing antibody titres to SIVmac239. Induction of SIV-specific immune responses was associated with increases in CD8+ T-cell proliferation and fluctuations in the levels of signal-joint T-cell receptor excision circles in peripheral blood cells. Five months after CD8+ T-cell depletion, only the two high-responding macaques were protected from intravenous challenge with pathogenic SIV, whilst the remaining animals were unable to control replication of the challenge virus. Together, these findings suggest that a transient period of enhanced antigenaemia during chronic SIV infection may serve to augment virus-specific immunity in some, but not all, macaques. These findings have relevance for induction of human immunodeficiency virus (HIV)-specific immune responses during prophylactic and therapeutic vaccination and for immunological evaluation of structured treatment interruptions in patients chronically infected with HIV-1.

Supplementary methods and a figure showing thymic output and peripheral CD8+ T-cell proliferation following in vivo CD8+ T-cell depletion are available in JGV Online.

{dagger}Present address: University of Erlangen-Nuremberg, Institute of Clinical and Molecular Virology, Schlossgarten 4, 91054 Erlangen, Germany.

{ddagger}Present address: Brigham and Women's Hospital, Harvard University School of Medicine, 25 Shattock Street, Boston, MA 02115, USA.

§Present address: Department of Microbiology and Immunology, HB 7900, Dartmouth Medical School, One Medical Center Drive, Lebanon, NH 03756, USA.




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