Evaluation of CD8+ T-cell and antibody responses following transient increased viraemia in rhesus macaques infected with live, attenuated simian immunodeficiency virus.
In vivo depletion of CD8+ T cells results in an increase in viral load in macaques chronically infected with simian immunodeficiency virus (SIVmac239deltanef). Here, the cellular and humoral immune responses associated with this transient period of enhanced viraemia in macaques infected with SIVmac239deltanef 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-ecreting 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.
Metzner
Karin J
KJ
Aaron Diamond AIDS Research Center and The Rockefeller University, New York, NY 10016, USA.
Moretto
Walter J
WJ
Gladstone Institute of Virology and Immunology, University of California, San Francisco, CA 94103, USA.
Donahoe
Sean M
SM
Aaron Diamond AIDS Research Center and The Rockefeller University, New York, NY 10016, USA.
Jin
Xia
X
University of Rochester Medicine Center, 601 Elmwood Avenue, Box 689, Rochester, NY 14642, USA.
Gettie
Agegnehu
A
Aaron Diamond AIDS Research Center and The Rockefeller University, New York, NY 10016, USA.
Montefiori
David C
DC
Center for AIDS Research, Department of Surgery, Duke University Medical Center, Durham, NC 27710, USA.
Marx
Preston A
PA
Tulane Regional Primate Research Center and Department of Tropical Medicine, Tulane University Health Sciences Center, Covington, LA 70433, USA.
Binley
James M
JM
Torrey Pines Institute for Molecular Studies, 3550 General Atomics Court, San Diego, CA 92121, USA.
Nixon
Douglas F
DF
Gladstone Institute of Virology and Immunology, University of California, San Francisco, CA 94103, USA.
Connor
Ruth I
RI
Aaron Diamond AIDS Research Center and The Rockefeller University, New York, NY 10016, USA.
D000818:Animals; D000914:Antibodies, Viral / Q000097:blood / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D004797:Enzyme-Linked Immunosorbent Assay; D015686:Gene Products, env / Q000276:immunology; D015683:Gene Products, gag / Q000276:immunology; D008212:Lymphocyte Depletion; D008253:Macaca mulatta; D009500:Neutralization Tests; D012367:RNA, Viral / Q000097:blood; D016097:Simian Acquired Immunodeficiency Syndrome / Q000276:immunology*; D015302:Simian Immunodeficiency Virus / Q000276:immunology*; D014766:Viremia / Q000276:immunology
D000914:Antibodies, Viral; C066594:Gag protein p27, Simian immunodeficiency virus; D015686:Gene Products, env; D015683:Gene Products, gag; D012367:RNA, Viral; C078684:simian immunodeficiency virus gp130