CD4+ Th17 and Treg Subsets During Acute/Early HIV Infection are Associated with Distinct Patterns of Disease Progression and anti-HIV CD8+ Responses

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

Barcelona

Conferencia; AIDS Vaccine Conference; 2013

Background: Th17 and Treg subsets have been related to HIV/SIV disease progression. Their role and direct relation with specific HIV-adaptive T-cell responses during primary HIV-infection (PHI) are largely unexplored topics. Aim: To analyze Th17 and Treg subsets, their balance and correlation with clinical parameters and specific anti-HIV responses during acute/early infection.  Methods: PBMCs were obtained from 6 healthy donors (HDs) and 22 HIV infected-subjects: 6 elite controllers (ECs), 4 chronics, and 12 PHIs (within 6 months post-infection (mpi)). PHIs were classified as ?PHI<350? if CD4-counts dropped below 350 cells/ul within 12 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/intra-groups and correlated to viral load (VL) and CD4-counts (baseline, set-point and 12 mpi), and specific anti-HIV CD8+ responses, using parametric and non-parametric statistics.  Results: Baseline CD4 (p=0.0669, r=0.3885) and set-point (p=0.0486, r=0.5) counts were directly correlated with baseline Th17 absolute counts, which were found to be higher in PHI>350 vs. PHI<350. Moreover, VL levels at 12 mpi inversely correlated with baseline (p=0.0406, r=-0.5965) and 12 mpi (p=0.0208, r=-0.6309) %Th17. Th17/Tregs ratio was higher for HDs compared to any HIV+ group (p<0.01), and within PHIs Th17/Tregs was directly associated with CD4-counts at 12 mpi (p=0.0167, r=0.7928). Significantly, Th17 and quality of anti-HIV T-CD8+ responses were directly associated, thus higher baseline %Th17 correlated with a higher CD8+-mediated viral inhibitory activity at 12 mpi (p=0.0036, r=0.8289). Moreover, Th17 counts at 12 mpi also related with anti-HIV CD8+ responses (% of HIV CD8+/CD107+/IFN-gamma+ cells, p= 0.0238, r=0.8469).  Conclusion: Results suggest that higher counts and frequency of Th17 and Th17/Tregs ratio at early stages after HIV-infection are associated with slower disease progression in terms of clinical parameters. Importantly, preservation of Th17 compartment associates with the capacity to exert specific anti-HIV CD8+ responses at later times post-infection.