Th17 and Th17/Treg ratio at early HIV infection associate with protective HIV-specific CD8+ T-cell responses and disease progression

Juliana Falivene; Yanina Ghiglione; Natalia Laufer; María Eugenia Socías; María Pía Holgado; María Julia Ruiz; Cynthia Maeto; María Inés Figueroa; Luis D. Giavedoni; Pedro Cahn; Horacio Salomón; Omar Sued; Gabriela Turk; María Magdalena Gherardi

doi:10.1038/srep11511

Th17 and Th17/Treg ratio at early HIV infection associate with protective HIV-specific CD8⁺ T-cell responses and disease progression

Juliana Falivene, Yanina Ghiglione, Natalia Laufer, María Eugenia Socías, María Pía Holgado, María Julia Ruiz, Cynthia Maeto, María Inés Figueroa, Luis D. Giavedoni, Pedro Cahn, Horacio Salomón, Omar Sued, Gabriela Turk, María Magdalena Gherardi

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Abstract

The aim of this study was to analyze Th17 and Treg subsets and their correlation with anti-HIV T-cell responses and clinical parameters during (acute/early) primary HIV infection (PHI) and up to one year post-infection (p.i). Samples from 14 healthy donors (HDs), 40 PHI patients, 17 Chronics, and 13 Elite controllers (ECs) were studied. The percentages of Th17 and Treg subsets were severely altered in Chronics, whereas all HIV-infected individuals (including ECs) showed Th17/Treg imbalance compared to HDs, in concordance with higher frequencies of activated CD8⁺ T-cells (HLA-DR⁺/CD38⁺). Better clinical status (higher CD4 counts, lower viral loads and activation) was associated with higher Th17 and lower Treg levels. We found positive correlations between Th17 at baseline and anti-HIV CD8⁺ T-cell functionality: viral inhibitory activity (VIA) and key polyfunctions (IFN-γ⁺/CD107_A/B⁺) at both early and later times p.i, highlighting the prognostic value of Th17 cells to preserve an effective HIV T-cell immunity. Th17/Treg ratio and the IL-17 relative mean fluorescence intensity (rMFI of IL-17) were also positively correlated with VIA. Taken together, our results suggested a potential link between Th17 and Th17/Treg ratio with key HIV-specific CD8⁺ T-cell responses against the infection.

Original language	English (US)
Article number	11511
Journal	Scientific reports
Volume	5
DOIs	https://doi.org/10.1038/srep11511
State	Published - Jun 23 2015

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Falivene, J., Ghiglione, Y., Laufer, N., Socías, M. E., Holgado, M. P., Ruiz, M. J., Maeto, C., Figueroa, M. I., Giavedoni, L. D., Cahn, P., Salomón, H., Sued, O., Turk, G., & Gherardi, M. M. (2015). Th17 and Th17/Treg ratio at early HIV infection associate with protective HIV-specific CD8⁺ T-cell responses and disease progression. Scientific reports, 5, [11511]. https://doi.org/10.1038/srep11511

Th17 and Th17/Treg ratio at early HIV infection associate with protective HIV-specific CD8⁺ T-cell responses and disease progression. / Falivene, Juliana; Ghiglione, Yanina; Laufer, Natalia; Socías, María Eugenia; Holgado, María Pía; Ruiz, María Julia; Maeto, Cynthia; Figueroa, María Inés; Giavedoni, Luis D.; Cahn, Pedro; Salomón, Horacio; Sued, Omar; Turk, Gabriela; Gherardi, María Magdalena.

In: Scientific reports, Vol. 5, 11511, 23.06.2015.

Research output: Contribution to journal › Article › peer-review

Falivene, J, Ghiglione, Y, Laufer, N, Socías, ME, Holgado, MP, Ruiz, MJ, Maeto, C, Figueroa, MI, Giavedoni, LD, Cahn, P, Salomón, H, Sued, O, Turk, G & Gherardi, MM 2015, 'Th17 and Th17/Treg ratio at early HIV infection associate with protective HIV-specific CD8⁺ T-cell responses and disease progression', Scientific reports, vol. 5, 11511. https://doi.org/10.1038/srep11511

Falivene, Juliana ; Ghiglione, Yanina ; Laufer, Natalia ; Socías, María Eugenia ; Holgado, María Pía ; Ruiz, María Julia ; Maeto, Cynthia ; Figueroa, María Inés ; Giavedoni, Luis D. ; Cahn, Pedro ; Salomón, Horacio ; Sued, Omar ; Turk, Gabriela ; Gherardi, María Magdalena. / Th17 and Th17/Treg ratio at early HIV infection associate with protective HIV-specific CD8⁺ T-cell responses and disease progression. In: Scientific reports. 2015 ; Vol. 5.

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title = "Th17 and Th17/Treg ratio at early HIV infection associate with protective HIV-specific CD8+ T-cell responses and disease progression",

abstract = "The aim of this study was to analyze Th17 and Treg subsets and their correlation with anti-HIV T-cell responses and clinical parameters during (acute/early) primary HIV infection (PHI) and up to one year post-infection (p.i). Samples from 14 healthy donors (HDs), 40 PHI patients, 17 Chronics, and 13 Elite controllers (ECs) were studied. The percentages of Th17 and Treg subsets were severely altered in Chronics, whereas all HIV-infected individuals (including ECs) showed Th17/Treg imbalance compared to HDs, in concordance with higher frequencies of activated CD8+ T-cells (HLA-DR+/CD38+). Better clinical status (higher CD4 counts, lower viral loads and activation) was associated with higher Th17 and lower Treg levels. We found positive correlations between Th17 at baseline and anti-HIV CD8+ T-cell functionality: viral inhibitory activity (VIA) and key polyfunctions (IFN-γ+/CD107A/B+) at both early and later times p.i, highlighting the prognostic value of Th17 cells to preserve an effective HIV T-cell immunity. Th17/Treg ratio and the IL-17 relative mean fluorescence intensity (rMFI of IL-17) were also positively correlated with VIA. Taken together, our results suggested a potential link between Th17 and Th17/Treg ratio with key HIV-specific CD8+ T-cell responses against the infection.",

author = "Juliana Falivene and Yanina Ghiglione and Natalia Laufer and Soc{\'i}as, {Mar{\'i}a Eugenia} and Holgado, {Mar{\'i}a P{\'i}a} and Ruiz, {Mar{\'i}a Julia} and Cynthia Maeto and Figueroa, {Mar{\'i}a In{\'e}s} and Giavedoni, {Luis D.} and Pedro Cahn and Horacio Salom{\'o}n and Omar Sued and Gabriela Turk and Gherardi, {Mar{\'i}a Magdalena}",

note = "Funding Information: This research was funded by grants from the Agencia Nacional de Promoci{\'o}n Cient{\'i}fica y Tecnol{\'o}gica (PICT grant numbers 2008/0549 and 2011/1658, and PICTO Glaxo: 2013-0036) and from Fundaci{\'o}n A. J. Roemmers to M.M.G, and the UBACyt grant number UBACyT 2013-2016 20020120200263BA to Gabriela Turk. Part of this investigation used resources which were supported by the Southwest National Primate Research Center grant P51 OD011133 from the Office of Research Infrastructure Programs (ORIP), National Institutes of Health (NIH). We are specially thanked to the “Grupo Argentino de Seroconversi{\'o}n”, and to Sergio Mazzini for helpful assistance during manuscript preparation. We also acknowledged to Dr. David Favre and Dr. Ver{\'o}nica E. Garc{\'i}a for their useful comments and critical reading of the manuscript. Publisher Copyright: {\textcopyright} 2015 Scientific Reports.",

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doi = "10.1038/srep11511",

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T1 - Th17 and Th17/Treg ratio at early HIV infection associate with protective HIV-specific CD8+ T-cell responses and disease progression

AU - Falivene, Juliana

AU - Ghiglione, Yanina

AU - Laufer, Natalia

AU - Socías, María Eugenia

AU - Holgado, María Pía

AU - Ruiz, María Julia

AU - Maeto, Cynthia

AU - Figueroa, María Inés

AU - Giavedoni, Luis D.

AU - Cahn, Pedro

AU - Salomón, Horacio

AU - Sued, Omar

AU - Turk, Gabriela

AU - Gherardi, María Magdalena

N1 - Funding Information: This research was funded by grants from the Agencia Nacional de Promoción Científica y Tecnológica (PICT grant numbers 2008/0549 and 2011/1658, and PICTO Glaxo: 2013-0036) and from Fundación A. J. Roemmers to M.M.G, and the UBACyt grant number UBACyT 2013-2016 20020120200263BA to Gabriela Turk. Part of this investigation used resources which were supported by the Southwest National Primate Research Center grant P51 OD011133 from the Office of Research Infrastructure Programs (ORIP), National Institutes of Health (NIH). We are specially thanked to the “Grupo Argentino de Seroconversión”, and to Sergio Mazzini for helpful assistance during manuscript preparation. We also acknowledged to Dr. David Favre and Dr. Verónica E. García for their useful comments and critical reading of the manuscript. Publisher Copyright: © 2015 Scientific Reports.

PY - 2015/6/23

Y1 - 2015/6/23

N2 - The aim of this study was to analyze Th17 and Treg subsets and their correlation with anti-HIV T-cell responses and clinical parameters during (acute/early) primary HIV infection (PHI) and up to one year post-infection (p.i). Samples from 14 healthy donors (HDs), 40 PHI patients, 17 Chronics, and 13 Elite controllers (ECs) were studied. The percentages of Th17 and Treg subsets were severely altered in Chronics, whereas all HIV-infected individuals (including ECs) showed Th17/Treg imbalance compared to HDs, in concordance with higher frequencies of activated CD8+ T-cells (HLA-DR+/CD38+). Better clinical status (higher CD4 counts, lower viral loads and activation) was associated with higher Th17 and lower Treg levels. We found positive correlations between Th17 at baseline and anti-HIV CD8+ T-cell functionality: viral inhibitory activity (VIA) and key polyfunctions (IFN-γ+/CD107A/B+) at both early and later times p.i, highlighting the prognostic value of Th17 cells to preserve an effective HIV T-cell immunity. Th17/Treg ratio and the IL-17 relative mean fluorescence intensity (rMFI of IL-17) were also positively correlated with VIA. Taken together, our results suggested a potential link between Th17 and Th17/Treg ratio with key HIV-specific CD8+ T-cell responses against the infection.

AB - The aim of this study was to analyze Th17 and Treg subsets and their correlation with anti-HIV T-cell responses and clinical parameters during (acute/early) primary HIV infection (PHI) and up to one year post-infection (p.i). Samples from 14 healthy donors (HDs), 40 PHI patients, 17 Chronics, and 13 Elite controllers (ECs) were studied. The percentages of Th17 and Treg subsets were severely altered in Chronics, whereas all HIV-infected individuals (including ECs) showed Th17/Treg imbalance compared to HDs, in concordance with higher frequencies of activated CD8+ T-cells (HLA-DR+/CD38+). Better clinical status (higher CD4 counts, lower viral loads and activation) was associated with higher Th17 and lower Treg levels. We found positive correlations between Th17 at baseline and anti-HIV CD8+ T-cell functionality: viral inhibitory activity (VIA) and key polyfunctions (IFN-γ+/CD107A/B+) at both early and later times p.i, highlighting the prognostic value of Th17 cells to preserve an effective HIV T-cell immunity. Th17/Treg ratio and the IL-17 relative mean fluorescence intensity (rMFI of IL-17) were also positively correlated with VIA. Taken together, our results suggested a potential link between Th17 and Th17/Treg ratio with key HIV-specific CD8+ T-cell responses against the infection.

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Th17 and Th17/Treg ratio at early HIV infection associate with protective HIV-specific CD8⁺ T-cell responses and disease progression

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