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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

Th17 and Treg subsets among recently HIV-infected individuals that show different patterns of immune activation and disease progression.Comparison of baseline frequencies (right y axes) and absolute counts (left y axes) of Th17 (A) and Treg (B) cells between typical (TP, white symbols) and rapid (RP, black symbols) progressors. Baseline frequency of CD3+ CD8+ T-cells positive for CD38+ and HLA-DR+ activation markers was determined in TP and RP PHI sub-groups by flow cytometry (C). Frequency of activated CD8+ T-cells was determined for all groups (D). Boxes indicate median values with 25–75 percentiles and bars show the maximum and minimum values. Symbols represent individual patients within each group. The p values obtained are depicted as * p < 0.05, ** p < 0.01 and *** p < 0.001.
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f2: Th17 and Treg subsets among recently HIV-infected individuals that show different patterns of immune activation and disease progression.Comparison of baseline frequencies (right y axes) and absolute counts (left y axes) of Th17 (A) and Treg (B) cells between typical (TP, white symbols) and rapid (RP, black symbols) progressors. Baseline frequency of CD3+ CD8+ T-cells positive for CD38+ and HLA-DR+ activation markers was determined in TP and RP PHI sub-groups by flow cytometry (C). Frequency of activated CD8+ T-cells was determined for all groups (D). Boxes indicate median values with 25–75 percentiles and bars show the maximum and minimum values. Symbols represent individual patients within each group. The p values obtained are depicted as * p < 0.05, ** p < 0.01 and *** p < 0.001.

Mentions: First, we compared both baseline proportions and absolute counts of Th17 cells that were present in PHIs with a rapid immune deterioration (RPs) compared to those that showed a more typical progression pattern (TPs). Thereby, a trend to lower percentages of Th17 cells was found in RPs [0.13% (0.04–0.25) vs. 0.22% (0.06–0.40) in TPs; p = 0.13; Fig. 2A left y axis], in which also a significant lower baseline median absolute number of Th17 cells was evident [0.33 (0.10–0.63) cells/μl vs. 1.47 (0.40–3.14) cells/μl in TPs; p = 0.0040; Fig. 2A right y axis]. When the same analysis was extended to the Treg compartment, no significant differences were found [i.e Treg counts: 6.92 (2.26–13.17) cells/μl in TPs vs. 3.27 (1.43–5.53) cells/μl in RPs; p = 0.24; Fig. 2B]. Importantly, when the levels of CD8+ T-cell activation were analyzed in these two sub-groups, higher frequencies of activated CD8+ T-cells were found in RPs [30.1% (23.8–36.3) vs. 13.5% (6.5–23.8) in TPs; p = 0.0450; Fig. 2C]. We also corroborated that, as expected, HIV infection resulted in higher levels of CD8+ T-cell activation since early times p.i [15.2% (7.1–30.6) in baseline PHI samples] compared to both ECs [8.2% (3.2–12.8); p = 0.0460] and normal values found in HDs [0.38% (0.18–2.19); p = 0.0007; Fig. 2D]. And at one year p.i, although not significant, immune activation tended to decrease [6.5% (3.2–11.3) in one year p.i PHI samples]. Data from this part of the study indicated that, not only Chronics but also ECs showed higher immune activation levels than HDs (Fig. 2D), in concordance with their low Th17/Treg ratio (Fig. 1C).


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)

Th17 and Treg subsets among recently HIV-infected individuals that show different patterns of immune activation and disease progression.Comparison of baseline frequencies (right y axes) and absolute counts (left y axes) of Th17 (A) and Treg (B) cells between typical (TP, white symbols) and rapid (RP, black symbols) progressors. Baseline frequency of CD3+ CD8+ T-cells positive for CD38+ and HLA-DR+ activation markers was determined in TP and RP PHI sub-groups by flow cytometry (C). Frequency of activated CD8+ T-cells was determined for all groups (D). Boxes indicate median values with 25–75 percentiles and bars show the maximum and minimum values. Symbols represent individual patients within each group. 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

f2: Th17 and Treg subsets among recently HIV-infected individuals that show different patterns of immune activation and disease progression.Comparison of baseline frequencies (right y axes) and absolute counts (left y axes) of Th17 (A) and Treg (B) cells between typical (TP, white symbols) and rapid (RP, black symbols) progressors. Baseline frequency of CD3+ CD8+ T-cells positive for CD38+ and HLA-DR+ activation markers was determined in TP and RP PHI sub-groups by flow cytometry (C). Frequency of activated CD8+ T-cells was determined for all groups (D). Boxes indicate median values with 25–75 percentiles and bars show the maximum and minimum values. Symbols represent individual patients within each group. The p values obtained are depicted as * p < 0.05, ** p < 0.01 and *** p < 0.001.
Mentions: First, we compared both baseline proportions and absolute counts of Th17 cells that were present in PHIs with a rapid immune deterioration (RPs) compared to those that showed a more typical progression pattern (TPs). Thereby, a trend to lower percentages of Th17 cells was found in RPs [0.13% (0.04–0.25) vs. 0.22% (0.06–0.40) in TPs; p = 0.13; Fig. 2A left y axis], in which also a significant lower baseline median absolute number of Th17 cells was evident [0.33 (0.10–0.63) cells/μl vs. 1.47 (0.40–3.14) cells/μl in TPs; p = 0.0040; Fig. 2A right y axis]. When the same analysis was extended to the Treg compartment, no significant differences were found [i.e Treg counts: 6.92 (2.26–13.17) cells/μl in TPs vs. 3.27 (1.43–5.53) cells/μl in RPs; p = 0.24; Fig. 2B]. Importantly, when the levels of CD8+ T-cell activation were analyzed in these two sub-groups, higher frequencies of activated CD8+ T-cells were found in RPs [30.1% (23.8–36.3) vs. 13.5% (6.5–23.8) in TPs; p = 0.0450; Fig. 2C]. We also corroborated that, as expected, HIV infection resulted in higher levels of CD8+ T-cell activation since early times p.i [15.2% (7.1–30.6) in baseline PHI samples] compared to both ECs [8.2% (3.2–12.8); p = 0.0460] and normal values found in HDs [0.38% (0.18–2.19); p = 0.0007; Fig. 2D]. And at one year p.i, although not significant, immune activation tended to decrease [6.5% (3.2–11.3) in one year p.i PHI samples]. Data from this part of the study indicated that, not only Chronics but also ECs showed higher immune activation levels than HDs (Fig. 2D), in concordance with their low Th17/Treg ratio (Fig. 1C).

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