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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 the Th17 subset and other T-cell effector sub-populations measured upon polyclonal stimulation.Positive correlations between Th17 levels and polyclonal T-cell effector subsets found within PHI cohort: % of Th17 cells versus (vs.) Th1 (CD4 + IFN-γ + ) counts (A) and % of Tc17 (CD8 + IL-17 + ) cells (B) both at baseline; % of Th17 cells vs. % of Th1 cells (C) and % of Tc1 (CD8 + IFN-γ + ) cells (D) both at one year p.i. Polyclonal T-cell effector sub-populations were determined by flow cytometry after 6 hours of stimulation with a mixture of anti-CD3/anti-CD28 antibodies as described in Materials and Methods. 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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f5: Correlations between the Th17 subset and other T-cell effector sub-populations measured upon polyclonal stimulation.Positive correlations between Th17 levels and polyclonal T-cell effector subsets found within PHI cohort: % of Th17 cells versus (vs.) Th1 (CD4 + IFN-γ + ) counts (A) and % of Tc17 (CD8 + IL-17 + ) cells (B) both at baseline; % of Th17 cells vs. % of Th1 cells (C) and % of Tc1 (CD8 + IFN-γ + ) cells (D) both at one year p.i. Polyclonal T-cell effector sub-populations were determined by flow cytometry after 6 hours of stimulation with a mixture of anti-CD3/anti-CD28 antibodies as described in Materials and Methods. 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: In Fig. 5 it can be seen that baseline Th17 frequencies in PHIs were directly correlated with Th1 counts (p = 0.0085 r = 0.4504; Fig. 5A) and also with proportions of Tc17 cells (p = 0.0002 r = 0.5980; Fig. 5B) both at baseline. When these analyses were performed in samples obtained at one year p.i, we also found a direct correlation between Th17 cells and frequencies of Th1 (p = 0.0009 r = 0.7458; Fig. 5C) and Tc1 (p = 0.0169 r = 0.6047; Fig. 5D) cells.


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 the Th17 subset and other T-cell effector sub-populations measured upon polyclonal stimulation.Positive correlations between Th17 levels and polyclonal T-cell effector subsets found within PHI cohort: % of Th17 cells versus (vs.) Th1 (CD4 + IFN-γ + ) counts (A) and % of Tc17 (CD8 + IL-17 + ) cells (B) both at baseline; % of Th17 cells vs. % of Th1 cells (C) and % of Tc1 (CD8 + IFN-γ + ) cells (D) both at one year p.i. Polyclonal T-cell effector sub-populations were determined by flow cytometry after 6 hours of stimulation with a mixture of anti-CD3/anti-CD28 antibodies as described in Materials and Methods. 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

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

f5: Correlations between the Th17 subset and other T-cell effector sub-populations measured upon polyclonal stimulation.Positive correlations between Th17 levels and polyclonal T-cell effector subsets found within PHI cohort: % of Th17 cells versus (vs.) Th1 (CD4 + IFN-γ + ) counts (A) and % of Tc17 (CD8 + IL-17 + ) cells (B) both at baseline; % of Th17 cells vs. % of Th1 cells (C) and % of Tc1 (CD8 + IFN-γ + ) cells (D) both at one year p.i. Polyclonal T-cell effector sub-populations were determined by flow cytometry after 6 hours of stimulation with a mixture of anti-CD3/anti-CD28 antibodies as described in Materials and Methods. 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: In Fig. 5 it can be seen that baseline Th17 frequencies in PHIs were directly correlated with Th1 counts (p = 0.0085 r = 0.4504; Fig. 5A) and also with proportions of Tc17 cells (p = 0.0002 r = 0.5980; Fig. 5B) both at baseline. When these analyses were performed in samples obtained at one year p.i, we also found a direct correlation between Th17 cells and frequencies of Th1 (p = 0.0009 r = 0.7458; Fig. 5C) and Tc1 (p = 0.0169 r = 0.6047; Fig. 5D) cells.

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