Reduced Protection from Simian Immunodeficiency Virus SIV mac251 Infection Afforded by Memory CD8 + T Cells Induced by Vaccination during CD4 + T-Cell Deficiency

ABSTRACT Adaptive CD4 + and CD8 + T-cell responses have been associated with control of human immunodeficiency virus/simian immunodeficiency virus (HIV/SIV) replication. Here, we have designed a study with Indian rhesus macaques to more directly assess the role of CD8 SIV-specific responses in contr...

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Published in:Journal of virology 2008-10, Vol.82 (19), p.9629-9638
Main Authors: Vaccari, Monica, Mattapallil, Joseph, Song, Kaimei, Tsai, Wen-Po, Hryniewicz, Anna, Venzon, David, Zanetti, Maurizio, Reimann, Keith A., Roederer, Mario, Franchini, Genoveffa
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Language:English
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Summary:ABSTRACT Adaptive CD4 + and CD8 + T-cell responses have been associated with control of human immunodeficiency virus/simian immunodeficiency virus (HIV/SIV) replication. Here, we have designed a study with Indian rhesus macaques to more directly assess the role of CD8 SIV-specific responses in control of viral replication. Macaques were immunized with a DNA prime-modified vaccinia virus Ankara (MVA)-SIV boost regimen under normal conditions or under conditions of antibody-induced CD4 + T-cell deficiency. Depletion of CD4 + cells was performed in the immunized macaques at the peak of SIV-specific CD4 + T-cell responses following the DNA prime dose. A group of naïve macaques was also treated with the anti-CD4 depleting antibody as a control, and an additional group of macaques immunized under normal conditions was depleted of CD8 + T cells prior to challenge exposure to SIV mac251 . Analysis of the quality and quantity of vaccine-induced CD8 + T cells demonstrated that SIV-specific CD8 + T cells generated under conditions of CD4 + T-cell deficiency expressed low levels of Bcl-2 and interleukin-2 (IL-2), and plasma virus levels increased over time. Depletion of CD8 + T cells prior to challenge exposure abrogated vaccine-induced protection as previously shown. These data support the notion that adaptive CD4 + T cells are critical for the generation of effective CD8 + T-cell responses to SIV that, in turn, contribute to protection from AIDS. Importantly, they also suggest that long-term protection from disease will be afforded only by T-cell vaccines for HIV that provide a balanced induction of CD4 + and CD8 + T-cell responses and protect against early depletion of CD4 + T cells postinfection.
ISSN:0022-538X
1098-5514
DOI:10.1128/JVI.00893-08