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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

Alteration of Th17 and Treg subsets and Th17/Treg ratio at different stages of HIV infection.PBMCs were stimulated for 6 hours with anti-CD3/anti-CD28 or medium alone (background control) prior to intracellular staining. Background subtracted values of CD3+ CD4+ IL-17+ producing cells (Th17) are shown (A). Intranuclear staining for detection of CD3+ CD4+ CD25+ FoxP3+ cells (Tregs, B). Th17/Treg ratio was calculated for each patient (C). Boxes indicate median values with 25–75 percentiles and bars show the maximum and minimum values. Symbols represent individual patients: Healthy donors (Δ, HDs), Chronics (◊), Elite controllers (□, ECs) and primary HIV infection (PHI) cohort at baseline and one year p.i follow up (◦, typical progressors or TPs with CD4 counts above 350 cells/μl during the first year p.i; ∑, rapid progressors or RPs with CD4 counts below 350 cells/μl during the first year p.i). The p values obtained are depicted as * p < 0.05, ** p < 0.01 and *** p < 0.001.
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f1: Alteration of Th17 and Treg subsets and Th17/Treg ratio at different stages of HIV infection.PBMCs were stimulated for 6 hours with anti-CD3/anti-CD28 or medium alone (background control) prior to intracellular staining. Background subtracted values of CD3+ CD4+ IL-17+ producing cells (Th17) are shown (A). Intranuclear staining for detection of CD3+ CD4+ CD25+ FoxP3+ cells (Tregs, B). Th17/Treg ratio was calculated for each patient (C). Boxes indicate median values with 25–75 percentiles and bars show the maximum and minimum values. Symbols represent individual patients: Healthy donors (Δ, HDs), Chronics (◊), Elite controllers (□, ECs) and primary HIV infection (PHI) cohort at baseline and one year p.i follow up (◦, typical progressors or TPs with CD4 counts above 350 cells/μl during the first year p.i; ∑, rapid progressors or RPs with CD4 counts below 350 cells/μl during the first year p.i). The p values obtained are depicted as * p < 0.05, ** p < 0.01 and *** p < 0.001.

Mentions: In Fig. 1A it can be seen that the median percentage (IQR) of Th17 cells present in PHIs (both at baseline and one year follow-up, medians of 75 and 330 days p.i, respectively) were significantly higher compared to Chronics [0.17% (0.06–0.35) at baseline and 0.07% (0.05–0.22) at one year p.i in PHIs vs. 0.03% (0.01–0.07) in Chronics; p values 0.0002 and 0.0145, respectively]. Within the PHI cohort, a trend to a decrease in Th17 levels was observed with the advancement of the infection [0.17% (0.06–0.35) at baseline vs. 0.07% (0.05–0.22) at one year; p = 0.11]; however, differences did not reach significance probably due to the high data dispersion. Interestingly, no significant differences were found between PHIs at baseline and both HDs [0.14% (0.07–0.28)] and ECs [0.11% (0.07–0.15)]. As expected, Chronics showed the lowest Th17 levels. When analysis was done taking into account the absolute Th17 counts (number of cells/μl) similar and enhanced differences between groups were observed (data not shown).


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)

Alteration of Th17 and Treg subsets and Th17/Treg ratio at different stages of HIV infection.PBMCs were stimulated for 6 hours with anti-CD3/anti-CD28 or medium alone (background control) prior to intracellular staining. Background subtracted values of CD3+ CD4+ IL-17+ producing cells (Th17) are shown (A). Intranuclear staining for detection of CD3+ CD4+ CD25+ FoxP3+ cells (Tregs, B). Th17/Treg ratio was calculated for each patient (C). Boxes indicate median values with 25–75 percentiles and bars show the maximum and minimum values. Symbols represent individual patients: Healthy donors (Δ, HDs), Chronics (◊), Elite controllers (□, ECs) and primary HIV infection (PHI) cohort at baseline and one year p.i follow up (◦, typical progressors or TPs with CD4 counts above 350 cells/μl during the first year p.i; ∑, rapid progressors or RPs with CD4 counts below 350 cells/μl during the first year p.i). The p values obtained are depicted as * p < 0.05, ** p < 0.01 and *** p < 0.001.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

f1: Alteration of Th17 and Treg subsets and Th17/Treg ratio at different stages of HIV infection.PBMCs were stimulated for 6 hours with anti-CD3/anti-CD28 or medium alone (background control) prior to intracellular staining. Background subtracted values of CD3+ CD4+ IL-17+ producing cells (Th17) are shown (A). Intranuclear staining for detection of CD3+ CD4+ CD25+ FoxP3+ cells (Tregs, B). Th17/Treg ratio was calculated for each patient (C). Boxes indicate median values with 25–75 percentiles and bars show the maximum and minimum values. Symbols represent individual patients: Healthy donors (Δ, HDs), Chronics (◊), Elite controllers (□, ECs) and primary HIV infection (PHI) cohort at baseline and one year p.i follow up (◦, typical progressors or TPs with CD4 counts above 350 cells/μl during the first year p.i; ∑, rapid progressors or RPs with CD4 counts below 350 cells/μl during the first year p.i). The p values obtained are depicted as * p < 0.05, ** p < 0.01 and *** p < 0.001.
Mentions: In Fig. 1A it can be seen that the median percentage (IQR) of Th17 cells present in PHIs (both at baseline and one year follow-up, medians of 75 and 330 days p.i, respectively) were significantly higher compared to Chronics [0.17% (0.06–0.35) at baseline and 0.07% (0.05–0.22) at one year p.i in PHIs vs. 0.03% (0.01–0.07) in Chronics; p values 0.0002 and 0.0145, respectively]. Within the PHI cohort, a trend to a decrease in Th17 levels was observed with the advancement of the infection [0.17% (0.06–0.35) at baseline vs. 0.07% (0.05–0.22) at one year; p = 0.11]; however, differences did not reach significance probably due to the high data dispersion. Interestingly, no significant differences were found between PHIs at baseline and both HDs [0.14% (0.07–0.28)] and ECs [0.11% (0.07–0.15)]. As expected, Chronics showed the lowest Th17 levels. When analysis was done taking into account the absolute Th17 counts (number of cells/μl) similar and enhanced differences between groups were observed (data not shown).

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