Th17 and Tregs at Early HIV Infection Influence Disease Progression and HIV Specific CD8+ Responses

FALIVENE, J; GHIGLIONE, Y; LAUFER, N; SOCIAS, ME; RUIZ, MJ; CAHN, P; SUED, O; SALOMON, H; TURK, G; GHERARDI, MM

Boston

Conferencia; Conference on Retroviruses and Oportunistic Infections; 2014

Background: Th17 and Treg subsets have been related to HIV/SIV disease progression. Their role and direct relation with specific HIV-adaptive Tcell responses during primary HIV infection (PHI) are unexplored topics. Aim: To analyze the frequency and balance of Th17 and Treg subsets and thecorrelation with clinical parameters, immune activation and HIV-specific responses during early infection.Methodology: PBMCs were obtained from 6 healthy donors (HDs) and 28 HIV infected subjects: 6 elite controllers (ECs), 5 chronics (Chs) and 17 PHIs(within 6 months post-infection (mpi)). Th17 and Treg cells (baseline and 12 mpi samples) were identified as CD3+/CD4+ IL-17+ or CD25+/FoxP3+(respectively). Data was compared inter/intragroups and correlated to clinical parameters (viral load (VL), CD4 counts), CD4+ or CD8+ CD38+/HLA-DR+activated T cells and HIV-specific CD8+ responses (specifically a viral inhibitory activity (VIA) assay and intracellular cytokine staining (ICS) for IFN-gammaproduction and CD107a/b cytotoxicity markers) measured at baseline, 6 and 12 mpi, using parametric and nonparametric statistics.Results: Chs had lower % of Th17 cells compared to HDs and ECs (p=0.006 and 0.021 respectively), among which frequencies were similar (median0.14 vs 0.11 respectively). In PHI group, CD4 counts at 6 mpi directly correlated with baseline Th17 counts (p=0.048, r=0.5). Moreover, VL at 12 mpiinversely correlated with baseline % of Th17 (p=0.041, r=-0.596). Th17/Tregs ratio was higher for HDs compared to any HIV+ group (p<0.01), and withinPHIs Th17/Tregs was directly associated with CD4 counts at 12 mpi (p=0.017, r=0.793). Significantly, Th17 and quality of HIV-specific CD8+ responses,previously observed to be protective, were directly associated: higher basal % of Th17 correlated with higher CD8+-mediated VIA at 12 mpi (p=0.004,r=0.829) and Th17 counts at 12 mpi also related with % of HIV CD8+/CD107a/b+/IFN-gamma+ cells (p=0.024, r=0.847). Regarding immuneactivation, as expected HDs had the lowest and Chs the highest % of activated T cells compared to the other groups (p<0,05). Of note, in PHIs activationoccurs rapidly after infection and normalizes at 12 mpi (p=0,004). Importantly, Th17/Tregs ratio of groups altogether, negatively correlated with activatedCD8+ and CD4+ T cells (p<0.05), suggesting a proper balance is associated with a lower level of immune activation.Conclusions: Results indicate that higher counts and frequency of Th17 and higher Th17/Tregs ratio at early stages of HIV infection associate with slowerdisease progression in terms of clinical parameters and immune activation. Importantly, preservation of Th17 subset associates with the capacity to exertprotective HIV-specific CD8+ responses at later times post-infection.