Rapid perturbation in viremia levels drives increases in functional avidity of HIV-specific CD8 T cells.
The factors determining the functional avidity and its relationship with the broad heterogeneity of antiviral T cell responses remain partially understood. We investigated HIV-specific CD8 T cell responses in 85 patients with primary HIV infection (PHI) or chronic (progressive and non-progressive) i...
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oai:doaj.org-article:fdc4487162b047959a2bf1893a4732702021-11-18T06:05:26ZRapid perturbation in viremia levels drives increases in functional avidity of HIV-specific CD8 T cells.1553-73661553-737410.1371/journal.ppat.1003423https://doaj.org/article/fdc4487162b047959a2bf1893a4732702013-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/23853580/pdf/?tool=EBIhttps://doaj.org/toc/1553-7366https://doaj.org/toc/1553-7374The factors determining the functional avidity and its relationship with the broad heterogeneity of antiviral T cell responses remain partially understood. We investigated HIV-specific CD8 T cell responses in 85 patients with primary HIV infection (PHI) or chronic (progressive and non-progressive) infection. The functional avidity of HIV-specific CD8 T cells was not different between patients with progressive and non-progressive chronic infection. However, it was significantly lower in PHI patients at the time of diagnosis of acute infection and after control of virus replication following one year of successful antiretroviral therapy. High-avidity HIV-specific CD8 T cells expressed lower levels of CD27 and CD28 and were enriched in cells with an exhausted phenotype, i.e. co-expressing PD-1/2B4/CD160. Of note, a significant increase in the functional avidity of HIV-specific CD8 T cells occurred in early-treated PHI patients experiencing a virus rebound after spontaneous treatment interruption. This increase in functional avidity was associated with the accumulation of PD-1/2B4/CD160 positive cells, loss of polyfunctionality and increased TCR renewal. The increased TCR renewal may provide the mechanistic basis for the generation of high-avidity HIV-specific CD8 T cells. These results provide insights on the relationships between functional avidity, viremia, T-cell exhaustion and TCR renewal of antiviral CD8 T cell responses.Selena ViganòFelicitas Bellutti EndersIsabelle MiconnetCristina CelleraiAnne-Laure SavoyeVirginie RozotMatthieu PerreauMohamed FaouziKhalid OhmitiMatthias CavassiniPierre-Alexandre BartGiuseppe PantaleoAlexandre HarariPublic Library of Science (PLoS)articleImmunologic diseases. AllergyRC581-607Biology (General)QH301-705.5ENPLoS Pathogens, Vol 9, Iss 7, p e1003423 (2013) |
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| topic |
Immunologic diseases. Allergy RC581-607 Biology (General) QH301-705.5 |
| spellingShingle |
Immunologic diseases. Allergy RC581-607 Biology (General) QH301-705.5 Selena Viganò Felicitas Bellutti Enders Isabelle Miconnet Cristina Cellerai Anne-Laure Savoye Virginie Rozot Matthieu Perreau Mohamed Faouzi Khalid Ohmiti Matthias Cavassini Pierre-Alexandre Bart Giuseppe Pantaleo Alexandre Harari Rapid perturbation in viremia levels drives increases in functional avidity of HIV-specific CD8 T cells. |
| description |
The factors determining the functional avidity and its relationship with the broad heterogeneity of antiviral T cell responses remain partially understood. We investigated HIV-specific CD8 T cell responses in 85 patients with primary HIV infection (PHI) or chronic (progressive and non-progressive) infection. The functional avidity of HIV-specific CD8 T cells was not different between patients with progressive and non-progressive chronic infection. However, it was significantly lower in PHI patients at the time of diagnosis of acute infection and after control of virus replication following one year of successful antiretroviral therapy. High-avidity HIV-specific CD8 T cells expressed lower levels of CD27 and CD28 and were enriched in cells with an exhausted phenotype, i.e. co-expressing PD-1/2B4/CD160. Of note, a significant increase in the functional avidity of HIV-specific CD8 T cells occurred in early-treated PHI patients experiencing a virus rebound after spontaneous treatment interruption. This increase in functional avidity was associated with the accumulation of PD-1/2B4/CD160 positive cells, loss of polyfunctionality and increased TCR renewal. The increased TCR renewal may provide the mechanistic basis for the generation of high-avidity HIV-specific CD8 T cells. These results provide insights on the relationships between functional avidity, viremia, T-cell exhaustion and TCR renewal of antiviral CD8 T cell responses. |
| format |
article |
| author |
Selena Viganò Felicitas Bellutti Enders Isabelle Miconnet Cristina Cellerai Anne-Laure Savoye Virginie Rozot Matthieu Perreau Mohamed Faouzi Khalid Ohmiti Matthias Cavassini Pierre-Alexandre Bart Giuseppe Pantaleo Alexandre Harari |
| author_facet |
Selena Viganò Felicitas Bellutti Enders Isabelle Miconnet Cristina Cellerai Anne-Laure Savoye Virginie Rozot Matthieu Perreau Mohamed Faouzi Khalid Ohmiti Matthias Cavassini Pierre-Alexandre Bart Giuseppe Pantaleo Alexandre Harari |
| author_sort |
Selena Viganò |
| title |
Rapid perturbation in viremia levels drives increases in functional avidity of HIV-specific CD8 T cells. |
| title_short |
Rapid perturbation in viremia levels drives increases in functional avidity of HIV-specific CD8 T cells. |
| title_full |
Rapid perturbation in viremia levels drives increases in functional avidity of HIV-specific CD8 T cells. |
| title_fullStr |
Rapid perturbation in viremia levels drives increases in functional avidity of HIV-specific CD8 T cells. |
| title_full_unstemmed |
Rapid perturbation in viremia levels drives increases in functional avidity of HIV-specific CD8 T cells. |
| title_sort |
rapid perturbation in viremia levels drives increases in functional avidity of hiv-specific cd8 t cells. |
| publisher |
Public Library of Science (PLoS) |
| publishDate |
2013 |
| url |
https://doaj.org/article/fdc4487162b047959a2bf1893a473270 |
| work_keys_str_mv |
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