The HIV-1 Tat Protein Induces the Activation of CD8+ T Cells and Affects In Vivo the Magnitude and Kinetics of Antiviral Responses
| العنوان: | The HIV-1 Tat Protein Induces the Activation of CD8+ T Cells and Affects In Vivo the Magnitude and Kinetics of Antiviral Responses |
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| المؤلفون: | Barbara Ensoli, Peggy Marconi, Federica Destro, Riccardo Gavioli, Francesco Nicoli, Antonella Caputo, Mariaconcetta Sicurella, Eleonora Gallerani, Lara Rizzotto, Aurelio Cafaro, Valentina Finessi |
| المصدر: | PLoS ONE PLoS ONE, Vol 8, Iss 11, p e77746 (2013) |
| بيانات النشر: | Public Library of Science, 2013. |
| سنة النشر: | 2013 |
| مصطلحات موضوعية: | T cell, Priming (immunology), lcsh:Medicine, Herpesvirus 1, Human, Biology, CD8-Positive T-Lymphocytes, Lymphocyte Activation, Interleukin 21, Mice, Immune system, Chlorocebus aethiops, medicine, Cytotoxic T cell, Animals, Humans, lcsh:Science, Vero Cells, Mice, Inbred BALB C, Multidisciplinary, Innate immune system, lcsh:R, Herpes Simplex, Cell biology, Mice, Inbred C57BL, Kinetics, medicine.anatomical_structure, Immunology, Host-Pathogen Interactions, biology.protein, HIV-1, lcsh:Q, Female, tat Gene Products, Human Immunodeficiency Virus, Antibody, CD8, Research Article, T-Lymphocytes, Cytotoxic |
| الوصف: | 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. |
| اللغة: | English |
| تدمد: | 1932-6203 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::bd7682108bebc97cd80ff09879404709Test http://europepmc.org/articles/PMC3817196Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....bd7682108bebc97cd80ff09879404709 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 19326203 |
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