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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

Influence of Th17 levels and Th17/Treg ratio on the quality of the HIV-specific CD8 T-cell responses at later times post-infection.Differences between PHI patients showing baseline viral inhibitory activity (VIA) higher or lower to 25 percent (> and <25%, respectively) regarding to their CD4/CD8 ratio at baseline and one year p.i (A). Correlation found between VIA versus (vs.) relative mean fluorescent intensity (rMFI) of IL-17 within PHI cohort at one year p.i (B). Comparison of PHI patients with VIA > and <25% at one year p.i regarding to their rMFI of IL-17 also at one year p.i (C). Correlation found between VIA versus (vs.) Th17/Treg ratio within PHI cohort at one year p.i (D). Symbols distinguish individual patients from the different sub-groups indicated in the figure. PHI: primary HIV infection cohort. TPs: typical progressors. RPs: rapid progressors. Boxes indicate median values with 25–75 percentiles and bars show the maximum and minimum values. The p values obtained are depicted as * p < 0.05 (A and C). All r and p values correspond to Spearman’s correlations (B and D).
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f6: Influence of Th17 levels and Th17/Treg ratio on the quality of the HIV-specific CD8 T-cell responses at later times post-infection.Differences between PHI patients showing baseline viral inhibitory activity (VIA) higher or lower to 25 percent (> and <25%, respectively) regarding to their CD4/CD8 ratio at baseline and one year p.i (A). Correlation found between VIA versus (vs.) relative mean fluorescent intensity (rMFI) of IL-17 within PHI cohort at one year p.i (B). Comparison of PHI patients with VIA > and <25% at one year p.i regarding to their rMFI of IL-17 also at one year p.i (C). Correlation found between VIA versus (vs.) Th17/Treg ratio within PHI cohort at one year p.i (D). Symbols distinguish individual patients from the different sub-groups indicated in the figure. PHI: primary HIV infection cohort. TPs: typical progressors. RPs: rapid progressors. Boxes indicate median values with 25–75 percentiles and bars show the maximum and minimum values. The p values obtained are depicted as * p < 0.05 (A and C). All r and p values correspond to Spearman’s correlations (B and D).

Mentions: Next, we proceeded with the analysis of the possible relationships between Th17 levels, Th17 functionality (rMFI of IL-17) and Th17/Treg ratio vs. relevant anti-HIV CD8+ T-cell activities at later times p.i within the PHI cohort. The importance of evaluating the ex vivo VIA of CD8+ T-cells is reflected by the fact that it was probed to be predictive of the rate of CD4+ T-cell decline during HIV infection17. Importantly, when PHIs were sub-divided considering the magnitude of their CD8+ T-cell VIA, we found that PHI subjects with higher baseline VIA (>25%) showed significantly higher CD4/CD8 ratio compared to PHIs with lower VIA (<25%) at both, baseline and one year p.i (Fig. 6A). These results highlight the prognostic value of this antiviral CD8+ T-cell function as it was previously reported for other patient cohorts17. Then, it was interesting to find that Th17 functionality (evaluating rMFI of IL-17 as indicator of IL-17 production) was positively correlated with VIA (p = 0.0062 r = 0.7636; Fig. 6B). And in this case when samples were subdivided by their VIA levels (>25% or <25%), we detected significant differences between both groups, finding that in those patients with a higher VIA, higher rMFI of IL-17 was also detected [25.8 (21.8–31.5) for VIA>25% vs. 17.9 (12.9–19.8) for VIA<25%; p = 0.0206; Fig. 6C]. Finally, we also found a direct correlation between Th17/Treg ratio and VIA (p = 0.0120 r = 0.8649; Fig. 6D). Thus, PHI patients with a higher preservation of the Th17/Treg ratio showed HIV-specific CD8+ T-cells with superior capacity to suppress HIV replication in vitro.


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)

Influence of Th17 levels and Th17/Treg ratio on the quality of the HIV-specific CD8 T-cell responses at later times post-infection.Differences between PHI patients showing baseline viral inhibitory activity (VIA) higher or lower to 25 percent (> and <25%, respectively) regarding to their CD4/CD8 ratio at baseline and one year p.i (A). Correlation found between VIA versus (vs.) relative mean fluorescent intensity (rMFI) of IL-17 within PHI cohort at one year p.i (B). Comparison of PHI patients with VIA > and <25% at one year p.i regarding to their rMFI of IL-17 also at one year p.i (C). Correlation found between VIA versus (vs.) Th17/Treg ratio within PHI cohort at one year p.i (D). Symbols distinguish individual patients from the different sub-groups indicated in the figure. PHI: primary HIV infection cohort. TPs: typical progressors. RPs: rapid progressors. Boxes indicate median values with 25–75 percentiles and bars show the maximum and minimum values. The p values obtained are depicted as * p < 0.05 (A and C). All r and p values correspond to Spearman’s correlations (B and D).
© Copyright Policy - open-access
Related In: Results  -  Collection

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

f6: Influence of Th17 levels and Th17/Treg ratio on the quality of the HIV-specific CD8 T-cell responses at later times post-infection.Differences between PHI patients showing baseline viral inhibitory activity (VIA) higher or lower to 25 percent (> and <25%, respectively) regarding to their CD4/CD8 ratio at baseline and one year p.i (A). Correlation found between VIA versus (vs.) relative mean fluorescent intensity (rMFI) of IL-17 within PHI cohort at one year p.i (B). Comparison of PHI patients with VIA > and <25% at one year p.i regarding to their rMFI of IL-17 also at one year p.i (C). Correlation found between VIA versus (vs.) Th17/Treg ratio within PHI cohort at one year p.i (D). Symbols distinguish individual patients from the different sub-groups indicated in the figure. PHI: primary HIV infection cohort. TPs: typical progressors. RPs: rapid progressors. Boxes indicate median values with 25–75 percentiles and bars show the maximum and minimum values. The p values obtained are depicted as * p < 0.05 (A and C). All r and p values correspond to Spearman’s correlations (B and D).
Mentions: Next, we proceeded with the analysis of the possible relationships between Th17 levels, Th17 functionality (rMFI of IL-17) and Th17/Treg ratio vs. relevant anti-HIV CD8+ T-cell activities at later times p.i within the PHI cohort. The importance of evaluating the ex vivo VIA of CD8+ T-cells is reflected by the fact that it was probed to be predictive of the rate of CD4+ T-cell decline during HIV infection17. Importantly, when PHIs were sub-divided considering the magnitude of their CD8+ T-cell VIA, we found that PHI subjects with higher baseline VIA (>25%) showed significantly higher CD4/CD8 ratio compared to PHIs with lower VIA (<25%) at both, baseline and one year p.i (Fig. 6A). These results highlight the prognostic value of this antiviral CD8+ T-cell function as it was previously reported for other patient cohorts17. Then, it was interesting to find that Th17 functionality (evaluating rMFI of IL-17 as indicator of IL-17 production) was positively correlated with VIA (p = 0.0062 r = 0.7636; Fig. 6B). And in this case when samples were subdivided by their VIA levels (>25% or <25%), we detected significant differences between both groups, finding that in those patients with a higher VIA, higher rMFI of IL-17 was also detected [25.8 (21.8–31.5) for VIA>25% vs. 17.9 (12.9–19.8) for VIA<25%; p = 0.0206; Fig. 6C]. Finally, we also found a direct correlation between Th17/Treg ratio and VIA (p = 0.0120 r = 0.8649; Fig. 6D). Thus, PHI patients with a higher preservation of the Th17/Treg ratio showed HIV-specific CD8+ T-cells with superior capacity to suppress HIV replication in vitro.

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