Protection of Hepatocytes from Cytotoxic T Cell Mediated Killing by Interferon-Alpha

<p>Background: Cellular immunity plays a key role in determining the outcome of hepatitis C virus (HCV) infection, although the majority of infections become persistent. The mechanisms behind persistence are still not clear; however, the primary site of infection, the liver, may be critical. We investigated the ability of CD8+ T-cells (CTL) to recognise and kill hepatocytes under cytokine stimulation.</p> <p>Methods/Principle Findings: Resting hepatocytes cell lines expressed low levels of MHC Class I, but remained susceptible to CTL cytotoxicity. IFN-α treatment, in vitro, markedly increased hepatocyte MHC Class I expression, however, reduced sensitivity to CTL cytotoxicity. IFN-α stimulated hepatocyte lines were still able to present antigen and induce IFN-γ expression in interacting CTL. Resistance to killing was not due to the inhibition of the FASL/FAS- pathway, as stimulated hepatocytes were still susceptible to FAS-mediated apoptosis. In vitro stimulation with IFN-α, or the introduction of a subgenomic HCV replicon into the HepG2 line, upregulated the expression of the granzyme-B inhibitor–proteinase inhibitor 9 (PI-9). PI-9 expression was also observed in liver tissue biopsies from patients with chronic HCV infection.</p> <p>Conclusion/Significance: IFN-α induces resistance in hepatocytes to perforin/granzyme mediate CTL killing pathways. One possible mechanism could be through the expression of the PI-9. Hindrance of CTL cytotoxicity could contribute to the chronicity of hepatic viral infections.</p&gt

Optimization of the molecular sieving properties of amorphous SiCXNY:H hydrogen selective membranes prepared by PECVD

In this work, low frequency PECVD a-SiCxNy:H thin films have been synthesized in the temperature range 25–300 ∘C from hexamethyldisilazane precursor mixed with ammonia at various concentrations. A relevant correlation has been evidenced between the [N]/[C] atomic ratio in the gaseous phase and in the deposited thin films, allowing both prediction and control of the film microstructure. A simple method based on the analysis of the films FTIR spectra was proposed to determine the value of the [N]/[C] ratio and thus predict or adjust the gas transport properties of the membrane materials. Attractive ideal selectivities α*He/N2 exceeding 90 with He permeance ΠHe > 3.10−7 mol.s−1.m−2.Pa−1 were measured at 150 ∘C for the films prepared at 300 ∘C with an optimum [N]/[C] atomic ratio in the range 0.1–1.5. These films behave as molecular sieve membranes with a thermally activated transport of helium