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;...
| Main Authors: | , , , , , , , , , , , , , |
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| Format: | Journal article |
| Language: | English |
| Published: |
2007
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| _version_ | 1797106238457118720 |
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| author | Yang, H Dong, T Turnbull, E Ranasinghe, S Ondondo, B Goonetilleke, N Winstone, N di Gleria, K Bowness, P Conlon, C Borrow, P Hanke, T McMichael, A Dorrell, L |
| author_facet | Yang, H Dong, T Turnbull, E Ranasinghe, S Ondondo, B Goonetilleke, N Winstone, N di Gleria, K Bowness, P Conlon, C Borrow, P Hanke, T McMichael, A Dorrell, L |
| author_sort | Yang, H |
| collection | OXFORD |
| description | 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. |
| first_indexed | 2024-03-07T06:58:52Z |
| format | Journal article |
| id | oxford-uuid:ff0f57d2-5e22-43db-9195-475006170ef1 |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-07T06:58:52Z |
| publishDate | 2007 |
| record_format | dspace |
| spelling | oxford-uuid:ff0f57d2-5e22-43db-9195-475006170ef12022-03-27T13:41:40ZBroad TCR usage in functional HIV-1-specific CD8+ T cell expansions driven by vaccination during highly active antiretroviral therapy.Journal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:ff0f57d2-5e22-43db-9195-475006170ef1EnglishSymplectic Elements at Oxford2007Yang, HDong, TTurnbull, ERanasinghe, SOndondo, BGoonetilleke, NWinstone, Ndi Gleria, KBowness, PConlon, CBorrow, PHanke, TMcMichael, ADorrell, LDuring 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. |
| spellingShingle | Yang, H Dong, T Turnbull, E Ranasinghe, S Ondondo, B Goonetilleke, N Winstone, N di Gleria, K Bowness, P Conlon, C Borrow, P Hanke, T McMichael, A Dorrell, L Broad TCR usage in functional HIV-1-specific CD8+ T cell expansions driven by vaccination during highly active antiretroviral therapy. |
| title | Broad TCR usage in functional HIV-1-specific CD8+ T cell expansions driven by vaccination during highly active antiretroviral therapy. |
| title_full | Broad TCR usage in functional HIV-1-specific CD8+ T cell expansions driven by vaccination during highly active antiretroviral therapy. |
| title_fullStr | Broad TCR usage in functional HIV-1-specific CD8+ T cell expansions driven by vaccination during highly active antiretroviral therapy. |
| title_full_unstemmed | Broad TCR usage in functional HIV-1-specific CD8+ T cell expansions driven by vaccination during highly active antiretroviral therapy. |
| title_short | Broad TCR usage in functional HIV-1-specific CD8+ T cell expansions driven by vaccination during highly active antiretroviral therapy. |
| title_sort | broad tcr usage in functional hiv 1 specific cd8 t cell expansions driven by vaccination during highly active antiretroviral therapy |
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