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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
nef). Here, the cellular and humoral immune responses associated with this transient period of enhanced viraemia in macaques infected with SIVmac239
nef were characterized. Fourteen days after in vivo CD8+ T-cell depletion, two of six macaques experienced a 12 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.
Present address: University of Erlangen-Nuremberg, Institute of Clinical and Molecular Virology, Schlossgarten 4, 91054 Erlangen, Germany.
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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