Neutralizing antibodies as a potential secondary protective mechanism during chronic SHIV infection in CD8+ T-cell-depleted macaques.
OBJECTIVE
To directly examine the role of CD8+ T cells in controlling viremia and disease during chronic, low-level primate immunodeficiency virus infection in DNA prime/protein boost-vaccinated macaques.


BACKGROUND
A cohort of macaques, vaccinated with either a DNA prime/HIV-1 gp160 boost regimen or with gp160 alone was previously protected partially from sequential challenges with non-pathogenic and pathogenic strains of chimeric simian/human immunodeficiency virus (SHIV). In this study, the effect of temporary ablation of CD8+ T cells in these animals was examined.


METHODS
Animals were treated with an anti-CD8 antibody and CD8+ T-cell levels in peripheral blood, plasma viral loads, peripheral blood mononuclear cell-associated virus levels, neutralizing antibody (nAb) titers and simian immunodeficiency virus Gag-specific CD8+ T-cell numbers were followed.


RESULTS
Plasma viremia rose sharply in direct synchrony with a rapid but transient drop in CD8+ T cells. However, although levels of cell-associated virus also rose concomitantly, peak levels were much lower than those in virus-challenged, naive animals. In addition, despite a rise of pathogenic SHIV89.6P RNA levels in three animals, CD4+ T-cell counts remained unchanged. In each of these animals, neutralizing antibody titers against the pathogenic SHIV89.6P strain were high.


CONCLUSIONS
The results indicate that CD8+ T cells play a key role in suppressing viremia in a chronically infected host. In addition, the results suggest that in the absence of CD8+ T cells, nAb may act as an effective second line of defense by limiting both the spread of infectious virus to new target cells and CD4+ T-cell loss.
Rasmussen
Robert A
RA
Department of Cancer Immunology & AIDS, Dana-Farber Cancer Institute, Boston, Massachusetts 02115, USA.
Hofmann-Lehmann
Regina
R
Li
Pei-Lin
PL
Vlasak
Josef
J
Schmitz
Joern E
JE
Reimann
Keith A
KA
Kuroda
Marcelo J
MJ
Letvin
Norman L
NL
Montefiori
David C
DC
McClure
Harold M
HM
Ruprecht
Ruth M
RM
D000818:Animals; D000914:Antibodies, Viral / Q000276:immunology*; D001483:Base Sequence; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D002678:Chimera; D017931:DNA Primers; D004195:Disease Models, Animal; D006678:HIV / Q000276:immunology; D015658:HIV Infections / Q000276:immunology* / Q000821:virology; D008212:Lymphocyte Depletion; D008253:Macaca mulatta; D009500:Neutralization Tests; D015302:Simian Immunodeficiency Virus / Q000276:immunology; D014766:Viremia / Q000276:immunology
D000914:Antibodies, Viral; D017931:DNA Primers