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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 and Treg subsets with clinical parameters of disease progression.Correlations found among PHIs at baseline: Log CD4 counts versus (vs.) Log Th17 counts (A); plasma macrophage-derived chemokine (MDC) levels vs. % of Th17 cells (B); % of activated CD4 T-cells vs. relative mean fluorescence intensity (rMFI) of IL-17 (C) and % of Treg cells (D). Correlations found among PHIs at one year p.i follow up: Log CD4 counts vs. Log Th17 counts (E); baseline plasma soluble CD40 ligand (sCD40L) levels vs. Th17 counts at one year p.i (F); Log % of activated CD8 T-cells vs. Log % of Treg cells (G). Relationships present at chronic stages of HIV infection (Chronic, EC and PHI one year p.i samples): Log VL vs. Log Th17 counts (H) and % of Treg cells (I); Log CD4 counts vs. % of Treg cells (J). Soluble plasma proteins were determined by Luminex, for details see Materials and Methods. Symbols distinguish individual patients from the different groups indicated in the figure. ECs: Elite controllers. PHI: primary HIV infection cohort. TPs: typical progressors. RPs: rapid progressors. All r and p values shown correspond to Spearman’s correlations.
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f3: Correlations between Th17 and Treg subsets with clinical parameters of disease progression.Correlations found among PHIs at baseline: Log CD4 counts versus (vs.) Log Th17 counts (A); plasma macrophage-derived chemokine (MDC) levels vs. % of Th17 cells (B); % of activated CD4 T-cells vs. relative mean fluorescence intensity (rMFI) of IL-17 (C) and % of Treg cells (D). Correlations found among PHIs at one year p.i follow up: Log CD4 counts vs. Log Th17 counts (E); baseline plasma soluble CD40 ligand (sCD40L) levels vs. Th17 counts at one year p.i (F); Log % of activated CD8 T-cells vs. Log % of Treg cells (G). Relationships present at chronic stages of HIV infection (Chronic, EC and PHI one year p.i samples): Log VL vs. Log Th17 counts (H) and % of Treg cells (I); Log CD4 counts vs. % of Treg cells (J). Soluble plasma proteins were determined by Luminex, for details see Materials and Methods. Symbols distinguish individual patients from the different groups indicated in the figure. ECs: Elite controllers. PHI: primary HIV infection cohort. TPs: typical progressors. RPs: rapid progressors. All r and p values shown correspond to Spearman’s correlations.

Mentions: When we analyzed PHIs at baseline, a positive correlation between Th17 levels and CD4 counts (p = 0.0091 r = 0.4288; Fig. 3A) was observed, in concordance with a direct correlation between IL-17 plasma levels and CD4 counts (p = 0.0308 r = 0.4960; data not shown). Interestingly, a significant positive correlation was found between percentage of Th17 cells and plasma levels of the macrophage-derived chemokine (MDC; p = 0.0101 r = 0.5747; Fig. 3B), reinforced by another positive association of this chemokine with the rMFI of IL-17 (p = 0.0360 r = 0.4960; data not shown). Of note, MDC has been previously characterized to have HIV-suppressive activities15. On the other hand, the percentage of activated CD4+ T-cells was found to be inversely correlated with the rMFI of IL-17 (p = 0.0304 r = −0.5780; Fig. 3C) and, in contrast, directly associated with the percentage of Treg cells (p = 0.0246 r = 0.595; Fig. 3D).


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 and Treg subsets with clinical parameters of disease progression.Correlations found among PHIs at baseline: Log CD4 counts versus (vs.) Log Th17 counts (A); plasma macrophage-derived chemokine (MDC) levels vs. % of Th17 cells (B); % of activated CD4 T-cells vs. relative mean fluorescence intensity (rMFI) of IL-17 (C) and % of Treg cells (D). Correlations found among PHIs at one year p.i follow up: Log CD4 counts vs. Log Th17 counts (E); baseline plasma soluble CD40 ligand (sCD40L) levels vs. Th17 counts at one year p.i (F); Log % of activated CD8 T-cells vs. Log % of Treg cells (G). Relationships present at chronic stages of HIV infection (Chronic, EC and PHI one year p.i samples): Log VL vs. Log Th17 counts (H) and % of Treg cells (I); Log CD4 counts vs. % of Treg cells (J). Soluble plasma proteins were determined by Luminex, for details see Materials and Methods. Symbols distinguish individual patients from the different groups indicated in the figure. ECs: Elite controllers. PHI: primary HIV infection cohort. TPs: typical progressors. RPs: rapid progressors. All r and p values shown 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

f3: Correlations between Th17 and Treg subsets with clinical parameters of disease progression.Correlations found among PHIs at baseline: Log CD4 counts versus (vs.) Log Th17 counts (A); plasma macrophage-derived chemokine (MDC) levels vs. % of Th17 cells (B); % of activated CD4 T-cells vs. relative mean fluorescence intensity (rMFI) of IL-17 (C) and % of Treg cells (D). Correlations found among PHIs at one year p.i follow up: Log CD4 counts vs. Log Th17 counts (E); baseline plasma soluble CD40 ligand (sCD40L) levels vs. Th17 counts at one year p.i (F); Log % of activated CD8 T-cells vs. Log % of Treg cells (G). Relationships present at chronic stages of HIV infection (Chronic, EC and PHI one year p.i samples): Log VL vs. Log Th17 counts (H) and % of Treg cells (I); Log CD4 counts vs. % of Treg cells (J). Soluble plasma proteins were determined by Luminex, for details see Materials and Methods. Symbols distinguish individual patients from the different groups indicated in the figure. ECs: Elite controllers. PHI: primary HIV infection cohort. TPs: typical progressors. RPs: rapid progressors. All r and p values shown correspond to Spearman’s correlations.
Mentions: When we analyzed PHIs at baseline, a positive correlation between Th17 levels and CD4 counts (p = 0.0091 r = 0.4288; Fig. 3A) was observed, in concordance with a direct correlation between IL-17 plasma levels and CD4 counts (p = 0.0308 r = 0.4960; data not shown). Interestingly, a significant positive correlation was found between percentage of Th17 cells and plasma levels of the macrophage-derived chemokine (MDC; p = 0.0101 r = 0.5747; Fig. 3B), reinforced by another positive association of this chemokine with the rMFI of IL-17 (p = 0.0360 r = 0.4960; data not shown). Of note, MDC has been previously characterized to have HIV-suppressive activities15. On the other hand, the percentage of activated CD4+ T-cells was found to be inversely correlated with the rMFI of IL-17 (p = 0.0304 r = −0.5780; Fig. 3C) and, in contrast, directly associated with the percentage of Treg cells (p = 0.0246 r = 0.595; Fig. 3D).

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