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

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

Mar del Plata

Congreso; LIX Reunión Científica Anual de la SAIC en conjunto con la LXII Reunión Anual de la SAI; 2014

BACKGROUND: The direct relation of Th17 and Tregs with specific HIV-adaptive T cell responses during primary HIV infection (PHI) is unexplored. Aim: To analyze the frequency and balance of Th17 and Tregs and the correlation with clinical parameters, immune activation and HIV-specific responses during PHI. METHODOLOGY: We used PBMCs from 14 healthy donors (HDs) and 62 HIV+ patients: 13 elite controllers (ECs), 9 chronics (Chs) and 40 PHIs (baseline/year samples). Th17 and Tregs 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), CD8 CD38/HLA-DR activated cells and specific anti-HIV CD8 responses (a viral inhibitory activity (VIA) assay and ICS for IFNg production and CD107a/b cytotoxicity markers) using para/nonparametric statistics. RESULTS: Th17 and Tregs were altered in Chs versus (vs) HDs and ECs (p< 0.01), and all HIV+ patients had lower Th17/Tregs ratio vs HDs (p< 0.05). Among PHIs, according to their CD4 counts during the first year post-infection (pi), comparing rapid (RPs) vs typical (TPs) progression: at baseline RPs had higher immune activation (p=0.04), lower Th17 counts (p=0.004) and a tendency to higher VLs (p=0.07). Correlations with clinical parameters of disease progression were found: Th17 vs CD4 counts at baseline (p=0.002, r=0.499) and 1 year pi (p=0.007, r=0.596), Th17 vs soluble MDC at baseline (p=0.01, r=0.574) and sCD40L at 1 year pi (p=0.02, r= -0.648). Novel correlations with anti-HIV T-cell responses previously associated with protection were detected: Th17 cells vs baseline and 1 year pi HIV-specific polyfunctional IFN/CD107a/b cells (p=0.01, r=0.674 and p=0.03, r=0.605 respectively) and VIA at 1 year pi (p=0.06, r=0.572). CONCLUSIONS: Th17 preservation positively impacts on the clinical status of the HIV-infected patients. Remarkably, higher Th17 at early stages directly correlated with more potent anti-HIV T-cell responses associated with protection at later times pi.