Impact of HIV-ART on Th17 and Treg subpopulations in blood and genital mucosa

MARÍA PÍA HOLGADO; JULIANA FALIVENE; PAULA CARUSO; DIEGO H. ZURITA; NATALIA LAUFER; CARINA CASTRO; ÁNGELES NICO; YANINA GHIGLIONE; MARÍA JULIA RUIZ; PEDRO CAHN; OMAR SUED; GABRIELA TURK; VALERIA FINK; M. MAGDALENA GHERARDI

Durban

Conferencia; AIDS 2016. 21st International AIDS Conference; 2016

International AIDS Society

BACKGROUND: Th17 and Treg cells play a key role in HIV infection. It has been reported that after antiretroviral treatment (ART) only a partial restoration of Th17 and Th17/Treg frequencies can occurred in peripheral blood, a fact whichcan be more evident at intestinal mucosal level (1,2). However, the re-establishment of these T cell populations in female genital mucosa (FGM)after ART has been less studied. The AIM of the present study was to analyze these T-cell subsets in peripheral blood and FGM in different groups of patients.RESULTS: HIV+ ART- patients had significantly lower values of both Th17frequencies and Th17/Treg ratios compared to HDs [median%Th17 (HDs: 0.18 vs. HIV+ ART-: 0.05); median Th17/Treg ratio (HDs: 0.31vs. HIV+ART-: 0.03)]. After ART (HIV+ ART+) these parameterswere re-established (median %Th17: 0.45; median Th17/Treg ratio:0.39).Treg frequencies in HIV+ ART- patients were increased in relationto those detected in HDs, but in this case ART treatmentdid not restore Treg proportions (median %Treg HDs: 0.65, HIV+ART-: 0.97, HIV+ ART+: 1.05).HIV+ ART+ patients showed significant lower T cell activation levels of T CD4 and T CD8populations in comparison to HIV+ ART-. Even though, CD4 T cell activation remainedhigh in ART+ patients compared to HDs (median HD: 0.55 vs. HIV+ART+: 1.6; HIV+ART-: 2.73). CD4+ CD161+ cells had been defined as a gut-homing Th17 cell precursor population (3). We foundthat all HIV+ patients (ART- and ART+) presented a significant reduction of CD4+ CD161+ cellsin peripheral blood compared to HDs. Similar values of this T cell subset were found betweenHIV+ART+ and HIV+ART- patients. ART did not restore CD4+ CD161+ cells values in relation to HDs(median % CD4+ CD161+ HD: 13.58 vs. HIV+ART+: 8.78; HIV+ART-: 6.37). Cervical mononuclear cells from HIV+ patients secreted lower levels of IL-10 and IL-17Arespect to HDs. No differences were found between HIV+ ART- and HIV+ ART+ patients.A positive correlation was found between peripheral blood CD4+ CD161+ percentagesand CMCs IL-17F production in HDs (n=14) and HIV+ ART+ (n=12) patientsCONCLUSIONS* After ART, proportions of Th17 and Th17/Treg in peripheral blood were incremented, reaching similar values to those observed in HDs.* ART did not restore Treg proportions, which remained incremented compared to HDs.* Quantities of gut-homing Th17 precursors and secretion of IL-10 and IL-17A from CMCs of HIV+ ART+ were impared in comparison toHDs; suggesting that ART did not restore completely immune functions at mucosal level.* Positive correlation among CD4+ CD161+ cells and IL-17F production from CMCs may suggest a relation between the restoration of Th17cells at intestinal and genital mucosal tissues