Impact of art on the restoration of Th17 and Treg subpopulations in blood and genital mucosal compartments during HIV infection.

FALIVENE, J; HOLGADO. MP; ZURITA, D; LAUFER, N; FINK, V; CASTRO, CL; CARUSO, MP; OJEDA, LE; GHIGLIONE, Y; RUIZ, MJ; CAHN, P; SUED, O; TURK, G; GHERARDI, MM

Buenos Aires

Congreso; IV LASID Meeting, LXIII Argentinean Immunology Society Meeting, II French-Argentinean Immunology Meeting.; 2015

Th17 and Treg cells playa key role in HIV infection.Aim: to analyze the effect of antiretroviral therapy (ART) on theseT cell subsets in peripheral blood and female genital mucosa (FGM) in different patient groups.Groups: HIVneg (n=24); HIV+ART+ (>5 years on ART, n=11); HIV+ARTnaïve (n=15). Samples: Peripheral blood: PBMCs;FGM: Cervical mononuclear cells (CMCs).PBMCs: %Th17 in HIV+ART+ was higher vs HIV+ARTnaive(p<0.001), and reached values similar to HIVneg, whereassignificant lower %Th17 values were found in HIV+ARTnaive inrelation to the other groups. Th17/Treg ratios were also incremented after ART (HIV+ART+: medians: 0.22 vs HIV+ARTnaive: 0.03; p<0.01) reaching similar levels comparedto HIVneg (p=0.13). However, %Treg cells in HIV+ART+ and HIV+ARTnaive were comparable (1.52 and 0.97, respectively)and both higher than HIVneg (0.76; p<0.05). HIV+ART+ showed lower T-cell activation than HIV+ARTnaive (4.96 vs 11.66,p<0.002) but still remained at high levels (HIVneg: 3.11, p<0,01).Importantly, ART did not incrementCD4+/CD161+ counts (gut-homing Th17 precursor population), as no differences were found in HIV+ART+ vs HIV+ARTnaive and values found in oth groups were significantly lower compared to HIVneg. CMCs cytokine secretion: CMCs from IV+ART+ secreted lower levels of IL17A and IL-10 than HIVneg upon stimulation (IL-17A: 6.61 pg/ml vs 32.88 pg/ml, p<0.025; IL-10: 1.27 pg/ml vs 8.10 pg/ml, p<0.015).Results indicated that although after ART, proportions of Th17and Th17/Treg in peripheral blood were incremented, quantities of gut-homing Th17 precursors and IL-17A and IL-10 secretion fromCMCs were impaired compared to HIVneg, suggesting incomplete restoration of immune functions