Th17 and Th17/Treg ratio at early HIV infection associate with protective HIV-specific CD8(+) T-cell responses and disease progression.

Juliana Falivene,Yanina Ghiglione,María Julia Ruiz,María Inés Figueroa,Cynthia Maeto,Horacio Salomón,Natalia Laufer,Pedro Cahn,María Pía Holgado,María Magdalena Gherardi,Luis D Giavedoni,Gabriela Turk,Omar Sued,María Eugenia Socías

doi:10.1038/srep11511

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.

Highlights

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 primary HIV infection (PHI) and up to one year post-infection (p.i)
The different groups of HIV-infected participants selected to perform the present study were: a group of 40 individuals diagnosed during PHI (HIV seroconversion and/or within 6 months from presumed date of infection, 95% of them corresponded to Fiebig stages V and VI12), 17 typical chronically infected patients (Chronics), and a group of 13 infected individuals defined as Elite controllers (ECs)
We found that, compared to healthy donors (HDs), the Th17/Treg ratio was significantly reduced in all HIV-infected patients, and within the PHI cohort we found a rapid reduction in the Th17/Treg ratio

Summary

Introduction

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). Our results suggested a potential link between Th17 and Th17/Treg ratio with key HIV-specific CD8+ T-cell responses against the infection. The mechanisms and immune system components that contribute to the natural control of the infection and disease progression in some HIV-infected persons, in contrast to the vast majority of patients that undergo rapid progression, are not fully elucidated. RPs and TPs distinguish PHIs that had CD4 counts below or above 350 cells/μ l during the first year post-infection, respectively. CFlow cytometry double plataform, FACSCanto, BD Biosciences All these previous studies indicate that both Th17 cells and the Th17/Treg ratio have a critical role during HIV-1 infection. An evaluation of the possible correlations between these parameters and the HIV-specific antiviral adaptive T-cell response is still needed

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