Liver fibrosis in HIV/HCV co-infected individuals: NK reduced cytotoxicity is not associated to a dysfunctional LT-CD4+ cell stimulation

SISTO A; AVILA M; MARÍA LAURA POLO; MARTINEZ A; LAUFER NATALIA; ALEJANDRA URIOSTE; PEREZ H

Mar del Plata

Congreso; LXVI Reunion Anual SAI; 2018

Natural killer (NK) cells ameliorate liver fibrosis by killing activated hepatic stellate cells. We have demonstrated in HCV/HIV co-infected patients with advanced liver fibrosis that functionality of peripheral blood NK cells is significantly affected. Since LT-CD4+ modulate NK cell activity, we aimed to evaluate LT-CD4+ regulation of NK cell functionality in HCV/HIV coinfected patients with different stages of liver fibrosis.LT-CD4+ cells were purified from cryopreserved PBMCs from 30 HCV/HIV+ patients with mild or advanced fibrosis (METAVIR F0/F1 and F4, respectively). Similarly, NK cells were purified from one healthy volunteer. LT-CD4+ were stimulated with anti-CD3/CD28 beads at three different bead-to-cell ratios (1:1 48h, 1:5 and 1:35 24h), and conditioned medium (CM) were collected. Healthy NK cells were pre-activated with CM or vehicle overnight, followed by co-culture with K562 cells. CD107a externalization, and intracellular IFN-γ and TNF-α were measure by FC. Data was analysed using non-parametric statistics. Frequency of CD107a+ NK cells progressively increased as the intensity of LT-CD4+ stimulation was incremented (p