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The HIV-1 Tat Protein Induces the Activation of CD8(+) T Cells and Affects In Vivo the Magnitude and Kinetics of Antiviral Responses
T cells are functionally compromised during HIV infection despite their increased activation and proliferation. Although T cell hyperactivation is one of the best predictive markers for disease progression, its causes are poorly understood. Anti-tat natural immunity as well as anti-tat antibodies in...
Autores principales: | , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2013
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3817196/ https://www.ncbi.nlm.nih.gov/pubmed/24223723 http://dx.doi.org/10.1371/journal.pone.0077746 |
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author | Nicoli, Francesco Finessi, Valentina Sicurella, Mariaconcetta Rizzotto, Lara Gallerani, Eleonora Destro, Federica Cafaro, Aurelio Marconi, Peggy Caputo, Antonella Ensoli, Barbara Gavioli, Riccardo |
author_facet | Nicoli, Francesco Finessi, Valentina Sicurella, Mariaconcetta Rizzotto, Lara Gallerani, Eleonora Destro, Federica Cafaro, Aurelio Marconi, Peggy Caputo, Antonella Ensoli, Barbara Gavioli, Riccardo |
author_sort | Nicoli, Francesco |
collection | PubMed |
description | T cells are functionally compromised during HIV infection despite their increased activation and proliferation. Although T cell hyperactivation is one of the best predictive markers for disease progression, its causes are poorly understood. Anti-tat natural immunity as well as anti-tat antibodies induced by Tat immunization protect from progression to AIDS and reverse signs of immune activation in HIV-infected patients suggesting a role of Tat in T cell dysfunctionality. The Tat protein of HIV-1 is known to induce, in vitro, the activation of CD4(+) T lymphocytes, but its role on CD8(+) T cells and how these effects modulate, in vivo, the immune response to pathogens are not known. To characterize the role of Tat in T cell hyperactivation and dysfunction, we examined the effect of Tat on CD8(+) T cell responses and antiviral immunity in different ex vivo and in vivo models of antigenic stimulation, including HSV infection. We demonstrate for the first time that the presence of Tat during priming of CD8(+) T cells favors the activation of antigen-specific CTLs. Effector CD8(+) T cells generated in the presence of Tat undergo an enhanced and prolonged expansion that turns to a partial dysfunctionality at the peak of the response, and worsens HSV acute infection. Moreover, Tat favors the development of effector memory CD8(+) T cells and a transient loss of B cells, two hallmarks of the chronic immune activation observed in HIV-infected patients. Our data provide evidence that Tat affects CD8(+) T cell responses to co-pathogens and suggest that Tat may contribute to the CD8(+) T cell hyperactivation observed in HIV-infected individuals. |
format | Online Article Text |
id | pubmed-3817196 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2013 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-38171962013-11-09 The HIV-1 Tat Protein Induces the Activation of CD8(+) T Cells and Affects In Vivo the Magnitude and Kinetics of Antiviral Responses Nicoli, Francesco Finessi, Valentina Sicurella, Mariaconcetta Rizzotto, Lara Gallerani, Eleonora Destro, Federica Cafaro, Aurelio Marconi, Peggy Caputo, Antonella Ensoli, Barbara Gavioli, Riccardo PLoS One Research Article T cells are functionally compromised during HIV infection despite their increased activation and proliferation. Although T cell hyperactivation is one of the best predictive markers for disease progression, its causes are poorly understood. Anti-tat natural immunity as well as anti-tat antibodies induced by Tat immunization protect from progression to AIDS and reverse signs of immune activation in HIV-infected patients suggesting a role of Tat in T cell dysfunctionality. The Tat protein of HIV-1 is known to induce, in vitro, the activation of CD4(+) T lymphocytes, but its role on CD8(+) T cells and how these effects modulate, in vivo, the immune response to pathogens are not known. To characterize the role of Tat in T cell hyperactivation and dysfunction, we examined the effect of Tat on CD8(+) T cell responses and antiviral immunity in different ex vivo and in vivo models of antigenic stimulation, including HSV infection. We demonstrate for the first time that the presence of Tat during priming of CD8(+) T cells favors the activation of antigen-specific CTLs. Effector CD8(+) T cells generated in the presence of Tat undergo an enhanced and prolonged expansion that turns to a partial dysfunctionality at the peak of the response, and worsens HSV acute infection. Moreover, Tat favors the development of effector memory CD8(+) T cells and a transient loss of B cells, two hallmarks of the chronic immune activation observed in HIV-infected patients. Our data provide evidence that Tat affects CD8(+) T cell responses to co-pathogens and suggest that Tat may contribute to the CD8(+) T cell hyperactivation observed in HIV-infected individuals. Public Library of Science 2013-11-04 /pmc/articles/PMC3817196/ /pubmed/24223723 http://dx.doi.org/10.1371/journal.pone.0077746 Text en © 2013 Nicoli et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited. |
spellingShingle | Research Article Nicoli, Francesco Finessi, Valentina Sicurella, Mariaconcetta Rizzotto, Lara Gallerani, Eleonora Destro, Federica Cafaro, Aurelio Marconi, Peggy Caputo, Antonella Ensoli, Barbara Gavioli, Riccardo The HIV-1 Tat Protein Induces the Activation of CD8(+) T Cells and Affects In Vivo the Magnitude and Kinetics of Antiviral Responses |
title | The HIV-1 Tat Protein Induces the Activation of CD8(+) T Cells and Affects In Vivo the Magnitude and Kinetics of Antiviral Responses |
title_full | The HIV-1 Tat Protein Induces the Activation of CD8(+) T Cells and Affects In Vivo the Magnitude and Kinetics of Antiviral Responses |
title_fullStr | The HIV-1 Tat Protein Induces the Activation of CD8(+) T Cells and Affects In Vivo the Magnitude and Kinetics of Antiviral Responses |
title_full_unstemmed | The HIV-1 Tat Protein Induces the Activation of CD8(+) T Cells and Affects In Vivo the Magnitude and Kinetics of Antiviral Responses |
title_short | The HIV-1 Tat Protein Induces the Activation of CD8(+) T Cells and Affects In Vivo the Magnitude and Kinetics of Antiviral Responses |
title_sort | hiv-1 tat protein induces the activation of cd8(+) t cells and affects in vivo the magnitude and kinetics of antiviral responses |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3817196/ https://www.ncbi.nlm.nih.gov/pubmed/24223723 http://dx.doi.org/10.1371/journal.pone.0077746 |
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