Reduced protection from simian immunodeficiency virus SIVmac251 infection afforded by memory CD8+ T cells induced by vaccination during CD4+ T-cell deficiency
| Autor: | Monica, Vaccari, Joseph, Mattapallil, Kaimei, Song, Wen-Po, Tsai, Anna, Hryniewicz, David, Venzon, Maurizio, Zanetti, Keith A, Reimann, Mario, Roederer, Genoveffa, Franchini |
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| Rok vydání: | 2008 |
| Předmět: |
CD4-Positive T-Lymphocytes
viruses T-Lymphocytes Vaccination SAIDS Vaccines Simian Acquired Immunodeficiency Syndrome CD8-Positive T-Lymphocytes Macaca mulatta Ki-67 Antigen Phenotype Proto-Oncogene Proteins c-bcl-2 Vaccines and Antiviral Agents Animals Interleukin-2 Simian Immunodeficiency Virus Lymphocytes Cell Proliferation |
| Zdroj: | Journal of virology. 82(19) |
| ISSN: | 1098-5514 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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