Broad TCR Usage in Functional HIV-1-Specific CD8+ T Cell Expansions Driven by Vaccination during Highly Active Antiretroviral Therapy

During chronic HIV-1 infection, continuing viral replication is associated with impaired proliferative capacity of virus-specific CD8+ T cells and with the expansion and persistence of oligoclonal T cell populations. TCR usage may significantly influence CD8+ T cell-mediated control of AIDS viruses;...

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Bibliographic Details
Published in:The Journal of immunology (1950) 2007-07, Vol.179 (1), p.597-606
Main Authors: Yang, Hongbing, Dong, Tao, Turnbull, Emma, Ranasinghe, Srinika, Ondondo, Beatrice, Goonetilleke, Nilu, Winstone, Nicola, di Gleria, Kati, Bowness, Paul, Conlon, Christopher, Borrow, Persephone, Hanke, Tomas, McMichael, Andrew, Dorrell, Lucy
Format: Article
Language:English
Subjects:
AIDS Vaccines - administration & dosage
AIDS Vaccines - genetics
AIDS Vaccines - immunology
Antiretroviral Therapy, Highly Active
CD8-Positive T-Lymphocytes - immunology
CD8-Positive T-Lymphocytes - metabolism
CD8-Positive T-Lymphocytes - pathology
Cell Proliferation
Chronic Disease
Epitopes, T-Lymphocyte - administration & dosage
Epitopes, T-Lymphocyte - biosynthesis
Epitopes, T-Lymphocyte - genetics
Gene Products, gag - genetics
Gene Products, gag - immunology
Gene Products, nef - genetics
Gene Products, nef - immunology
Gene Products, pol - genetics
Gene Products, pol - immunology
Genes, T-Cell Receptor beta
HIV Infections - drug therapy
HIV Infections - immunology
HIV Infections - prevention & control
HIV-1 - genetics
HIV-1 - growth & development
HIV-1 - immunology
Humans
nef Gene Products, Human Immunodeficiency Virus
Receptors, Antigen, T-Cell, alpha-beta - biosynthesis
Receptors, Antigen, T-Cell, alpha-beta - genetics
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Summary:During chronic HIV-1 infection, continuing viral replication is associated with impaired proliferative capacity of virus-specific CD8+ T cells and with the expansion and persistence of oligoclonal T cell populations. TCR usage may significantly influence CD8+ T cell-mediated control of AIDS viruses; however, the potential to modulate the repertoire of functional virus-specific T cells by immunotherapy has not been explored. To investigate this, we analyzed the TCR Vbeta usage of CD8+ T cells populations which were expanded following vaccination with modified vaccinia virus Ankara expressing a HIV-1 gag/multiepitope immunogen (MVA.HIVA) in HIV-1-infected patients receiving highly active antiretroviral therapy. Vaccinations induced the re-expansion of HIV-1-specific CD8+ T cells and these showed broad TCR Vbeta usage which was maintained for at least 1 year in some individuals. By contrast, virus-specific CD8+ T cell populations in the same donors which failed to expand after vaccination and in unvaccinated controls were oligoclonal. Simultaneously, we observed that CD8+ T cells recognizing vaccine-derived HIV-1 epitopes displayed enhanced capacity to proliferate and to inhibit HIV-1 replication in vitro, following MVA.HIVA immunizations. Taken together, these data indicate that an attenuated viral-vectored vaccine can modulate adaptive CD8+ T cell responses to HIV-1 and improve their antiviral functional capacity. The potential therapeutic benefit of this vaccination approach warrants further investigation.
ISSN:0022-1767
1550-6606
DOI:10.4049/jimmunol.179.1.597