Liver Fibrosis in HIV/HCV coinfected individuals: NK reduced citotoxicity in not associated to a dysfunctional LT-CD4+ stimulation

ALEJANDRA URIOSTE; HECTOR PEREZ; ALICIA SISTO; MARIA AVILA; MARÍA L POLO; ANA MARTÍNEZ; NATALIA LAUFER

Conferencia; Reunión Conjunta SAIC SAI SAFIS; 2018

Natural killer (NK) cells ameliorate liver fibrosis by killing activatedhepatic stellate cells. We have demonstrated in HCV/HIV co-infectedpatients with advanced liver fibrosis that functionality of peripheralblood NK cells is significantly affected. Since LT-CD4+ modulateNK cell activity, we aimed to evaluate LT-CD4+ regulation of NK cellfunctionality in HCV/HIV coinfected patients with different stages ofliver fibrosis.LT-CD4+ cells were purified from cryopreserved PBMCs from 30HCV/HIV+ patients with mild or advanced fibrosis (METAVIR F0/F1 and F4, respectively). Similarly, NK cells were purified from onehealthy volunteer. LT-CD4+ were stimulated with anti-CD3/CD28beads at three different bead-to-cell ratios (1:1 48h, 1:5 and 1:3524h), and conditioned medium (CM) were collected. Healthy NKcells were pre-activated with CM or vehicle overnight, followed byco-culture with K562 cells. CD107a externalization, and intracellularIFN-γ and TNF-α were measure by FC. Data was analysed usingnon-parametric statistics.Frequency of CD107a+ NK cells progressively increased as the intensityof LT-CD4+ stimulation was incremented (p