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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.

Falivene J, Ghiglione Y, Laufer N, Eugenia Socías M, Pía Holgado M, Julia Ruiz M, Maeto C, Inés Figueroa M, Giavedoni LD, Cahn P, Salomón H, Sued O, Turk G, Magdalena Gherardi M - Sci Rep (2015)

Bottom Line: 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(+)).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.

View Article: PubMed Central - PubMed

Affiliation: Instituto de Investigaciones Biomédicas en Retrovirus y SIDA (INBIRS), Universidad de Buenos Aires-CONICET, Buenos Aires, Argentina.

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.

No MeSH data available.


Related in: MedlinePlus

Correlations between Th17 baseline levels and HIV-specific CD8 T-cell responses previously associated with protection.Positive correlations found within PHI cohort at baseline: % of Th17 cells versus (vs.) % of HIV-specific CD107A/B+ IFN-γ+ CD8 T-cells (A) and plasma IL-2 levels (C); Th17 counts vs. plasma MIP-1β levels (B). Correlations between baseline Th17 levels and anti-HIV specific responses at later times p.i within PHI group: baseline Th17 counts vs. % of HIV-specific CD107A/B+ IFN-γ+ CD8 T-cells (D), viral inhibitory activity (E) and % of HIV-specific PD-1+ CD8 T-cells all at one year p.i (F). Soluble plasma proteins were determined by Luminex. HIV-specific CD8 functionality was determined with different assays: one of them allowed the evaluation of CD8 T-cells with the capacity to degranulate and simultaneously secrete IFN-γ upon HIV-peptides stimulation by flow cytometry (A and D), other measured the overall CD8 T-cell capacity to inhibit in vitro HIV-1 replication in autologous CD4 T-cells (E), and the last one measured the expression of the exhaustion marker PD-1 on HIV-specific CD8 T-cells determined upon HIV-peptides stimulation by flow cytometry (F). These assays are described in detail in our previous publications1148. Symbols distinguish individual patients from the different sub-groups indicated in the figure. PHI: primary HIV infection cohort. TPs: typical progressors. RPs: rapid progressors. All r and p values correspond to Spearman’s correlations.
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f4: Correlations between Th17 baseline levels and HIV-specific CD8 T-cell responses previously associated with protection.Positive correlations found within PHI cohort at baseline: % of Th17 cells versus (vs.) % of HIV-specific CD107A/B+ IFN-γ+ CD8 T-cells (A) and plasma IL-2 levels (C); Th17 counts vs. plasma MIP-1β levels (B). Correlations between baseline Th17 levels and anti-HIV specific responses at later times p.i within PHI group: baseline Th17 counts vs. % of HIV-specific CD107A/B+ IFN-γ+ CD8 T-cells (D), viral inhibitory activity (E) and % of HIV-specific PD-1+ CD8 T-cells all at one year p.i (F). Soluble plasma proteins were determined by Luminex. HIV-specific CD8 functionality was determined with different assays: one of them allowed the evaluation of CD8 T-cells with the capacity to degranulate and simultaneously secrete IFN-γ upon HIV-peptides stimulation by flow cytometry (A and D), other measured the overall CD8 T-cell capacity to inhibit in vitro HIV-1 replication in autologous CD4 T-cells (E), and the last one measured the expression of the exhaustion marker PD-1 on HIV-specific CD8 T-cells determined upon HIV-peptides stimulation by flow cytometry (F). These assays are described in detail in our previous publications1148. Symbols distinguish individual patients from the different sub-groups indicated in the figure. PHI: primary HIV infection cohort. TPs: typical progressors. RPs: rapid progressors. All r and p values correspond to Spearman’s correlations.

Mentions: One of the major objectives of the present study was to analyze the potential impact that the proportions of Th17 and Tregs and alterations in their balance could have on the specific CD8+ T-cell responses with documented relevance on the antiviral HIV immunity. Therefore, our next aim was to analyze if baseline Th17 levels were related with specifc CD8+ T-cell functions previously associated with better clinical prognosis during HIV infection11. A significant positive correlation was observed between Th17 frequencies and proportions of HIV-specific CD107A/B+ IFN-γ+ CD8+ T-cells (p = 0.0161 r = 0.6749; Fig. 4A). Interestingly, in concordance with the hypothesis that a better T-cell immunity would be present in those patients with higher proportion of baseline Th17 cells,we found associations between the preservation of this subset with higher MIP-1β (T-cell chemokine associated with anti-viral properties; p = 0.0165 r = 0.5563; Fig. 4B) and also a trend to higher IL-2 plasma levels (T-cell homeostasis cytokine; p = 0.0537 r = 0.4617; Fig. 4C).


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

Falivene J, Ghiglione Y, Laufer N, Eugenia Socías M, Pía Holgado M, Julia Ruiz M, Maeto C, Inés Figueroa M, Giavedoni LD, Cahn P, Salomón H, Sued O, Turk G, Magdalena Gherardi M - Sci Rep (2015)

Correlations between Th17 baseline levels and HIV-specific CD8 T-cell responses previously associated with protection.Positive correlations found within PHI cohort at baseline: % of Th17 cells versus (vs.) % of HIV-specific CD107A/B+ IFN-γ+ CD8 T-cells (A) and plasma IL-2 levels (C); Th17 counts vs. plasma MIP-1β levels (B). Correlations between baseline Th17 levels and anti-HIV specific responses at later times p.i within PHI group: baseline Th17 counts vs. % of HIV-specific CD107A/B+ IFN-γ+ CD8 T-cells (D), viral inhibitory activity (E) and % of HIV-specific PD-1+ CD8 T-cells all at one year p.i (F). Soluble plasma proteins were determined by Luminex. HIV-specific CD8 functionality was determined with different assays: one of them allowed the evaluation of CD8 T-cells with the capacity to degranulate and simultaneously secrete IFN-γ upon HIV-peptides stimulation by flow cytometry (A and D), other measured the overall CD8 T-cell capacity to inhibit in vitro HIV-1 replication in autologous CD4 T-cells (E), and the last one measured the expression of the exhaustion marker PD-1 on HIV-specific CD8 T-cells determined upon HIV-peptides stimulation by flow cytometry (F). These assays are described in detail in our previous publications1148. Symbols distinguish individual patients from the different sub-groups indicated in the figure. PHI: primary HIV infection cohort. TPs: typical progressors. RPs: rapid progressors. All r and p values correspond to Spearman’s correlations.
© Copyright Policy - open-access
Related In: Results  -  Collection

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Show All Figures
getmorefigures.php?uid=PMC4477236&req=5

f4: Correlations between Th17 baseline levels and HIV-specific CD8 T-cell responses previously associated with protection.Positive correlations found within PHI cohort at baseline: % of Th17 cells versus (vs.) % of HIV-specific CD107A/B+ IFN-γ+ CD8 T-cells (A) and plasma IL-2 levels (C); Th17 counts vs. plasma MIP-1β levels (B). Correlations between baseline Th17 levels and anti-HIV specific responses at later times p.i within PHI group: baseline Th17 counts vs. % of HIV-specific CD107A/B+ IFN-γ+ CD8 T-cells (D), viral inhibitory activity (E) and % of HIV-specific PD-1+ CD8 T-cells all at one year p.i (F). Soluble plasma proteins were determined by Luminex. HIV-specific CD8 functionality was determined with different assays: one of them allowed the evaluation of CD8 T-cells with the capacity to degranulate and simultaneously secrete IFN-γ upon HIV-peptides stimulation by flow cytometry (A and D), other measured the overall CD8 T-cell capacity to inhibit in vitro HIV-1 replication in autologous CD4 T-cells (E), and the last one measured the expression of the exhaustion marker PD-1 on HIV-specific CD8 T-cells determined upon HIV-peptides stimulation by flow cytometry (F). These assays are described in detail in our previous publications1148. Symbols distinguish individual patients from the different sub-groups indicated in the figure. PHI: primary HIV infection cohort. TPs: typical progressors. RPs: rapid progressors. All r and p values correspond to Spearman’s correlations.
Mentions: One of the major objectives of the present study was to analyze the potential impact that the proportions of Th17 and Tregs and alterations in their balance could have on the specific CD8+ T-cell responses with documented relevance on the antiviral HIV immunity. Therefore, our next aim was to analyze if baseline Th17 levels were related with specifc CD8+ T-cell functions previously associated with better clinical prognosis during HIV infection11. A significant positive correlation was observed between Th17 frequencies and proportions of HIV-specific CD107A/B+ IFN-γ+ CD8+ T-cells (p = 0.0161 r = 0.6749; Fig. 4A). Interestingly, in concordance with the hypothesis that a better T-cell immunity would be present in those patients with higher proportion of baseline Th17 cells,we found associations between the preservation of this subset with higher MIP-1β (T-cell chemokine associated with anti-viral properties; p = 0.0165 r = 0.5563; Fig. 4B) and also a trend to higher IL-2 plasma levels (T-cell homeostasis cytokine; p = 0.0537 r = 0.4617; Fig. 4C).

Bottom Line: 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(+)).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.

View Article: PubMed Central - PubMed

Affiliation: Instituto de Investigaciones Biomédicas en Retrovirus y SIDA (INBIRS), Universidad de Buenos Aires-CONICET, Buenos Aires, Argentina.

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.

No MeSH data available.


Related in: MedlinePlus